Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3904G>T (p.Glu1302Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.3904G>T (p.Glu1302Ter)
Variation ID: 55045 Accession: VCV000055045.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091627 (GRCh38) [ NCBI UCSC ] 17: 41243644 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Aug 25, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3904G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1302Ter nonsense NM_001407571.1:c.3691G>T NP_001394500.1:p.Glu1231Ter nonsense NM_001407581.1:c.3904G>T NP_001394510.1:p.Glu1302Ter nonsense NM_001407582.1:c.3904G>T NP_001394511.1:p.Glu1302Ter nonsense NM_001407583.1:c.3904G>T NP_001394512.1:p.Glu1302Ter nonsense NM_001407585.1:c.3904G>T NP_001394514.1:p.Glu1302Ter nonsense NM_001407587.1:c.3901G>T NP_001394516.1:p.Glu1301Ter nonsense NM_001407590.1:c.3901G>T NP_001394519.1:p.Glu1301Ter nonsense NM_001407591.1:c.3901G>T NP_001394520.1:p.Glu1301Ter nonsense NM_001407593.1:c.3904G>T NP_001394522.1:p.Glu1302Ter nonsense NM_001407594.1:c.3904G>T NP_001394523.1:p.Glu1302Ter nonsense NM_001407596.1:c.3904G>T NP_001394525.1:p.Glu1302Ter nonsense NM_001407597.1:c.3904G>T NP_001394526.1:p.Glu1302Ter nonsense NM_001407598.1:c.3904G>T NP_001394527.1:p.Glu1302Ter nonsense NM_001407602.1:c.3904G>T NP_001394531.1:p.Glu1302Ter nonsense NM_001407603.1:c.3904G>T NP_001394532.1:p.Glu1302Ter nonsense NM_001407605.1:c.3904G>T NP_001394534.1:p.Glu1302Ter nonsense NM_001407610.1:c.3901G>T NP_001394539.1:p.Glu1301Ter nonsense NM_001407611.1:c.3901G>T NP_001394540.1:p.Glu1301Ter nonsense NM_001407612.1:c.3901G>T NP_001394541.1:p.Glu1301Ter nonsense NM_001407613.1:c.3901G>T NP_001394542.1:p.Glu1301Ter nonsense NM_001407614.1:c.3901G>T NP_001394543.1:p.Glu1301Ter nonsense NM_001407615.1:c.3901G>T NP_001394544.1:p.Glu1301Ter nonsense NM_001407616.1:c.3904G>T NP_001394545.1:p.Glu1302Ter nonsense NM_001407617.1:c.3904G>T NP_001394546.1:p.Glu1302Ter nonsense NM_001407618.1:c.3904G>T NP_001394547.1:p.Glu1302Ter nonsense NM_001407619.1:c.3904G>T NP_001394548.1:p.Glu1302Ter nonsense NM_001407620.1:c.3904G>T NP_001394549.1:p.Glu1302Ter nonsense NM_001407621.1:c.3904G>T NP_001394550.1:p.Glu1302Ter nonsense NM_001407622.1:c.3904G>T NP_001394551.1:p.Glu1302Ter nonsense NM_001407623.1:c.3904G>T NP_001394552.1:p.Glu1302Ter nonsense NM_001407624.1:c.3904G>T NP_001394553.1:p.Glu1302Ter nonsense NM_001407625.1:c.3904G>T NP_001394554.1:p.Glu1302Ter nonsense NM_001407626.1:c.3904G>T NP_001394555.1:p.Glu1302Ter nonsense NM_001407627.1:c.3901G>T NP_001394556.1:p.Glu1301Ter nonsense NM_001407628.1:c.3901G>T NP_001394557.1:p.Glu1301Ter nonsense NM_001407629.1:c.3901G>T NP_001394558.1:p.Glu1301Ter nonsense NM_001407630.1:c.3901G>T NP_001394559.1:p.Glu1301Ter nonsense NM_001407631.1:c.3901G>T NP_001394560.1:p.Glu1301Ter nonsense NM_001407632.1:c.3901G>T NP_001394561.1:p.Glu1301Ter nonsense NM_001407633.1:c.3901G>T NP_001394562.1:p.Glu1301Ter nonsense NM_001407634.1:c.3901G>T NP_001394563.1:p.Glu1301Ter nonsense NM_001407635.1:c.3901G>T NP_001394564.1:p.Glu1301Ter nonsense NM_001407636.1:c.3901G>T NP_001394565.1:p.Glu1301Ter nonsense NM_001407637.1:c.3901G>T NP_001394566.1:p.Glu1301Ter nonsense NM_001407638.1:c.3901G>T NP_001394567.1:p.Glu1301Ter nonsense NM_001407639.1:c.3904G>T NP_001394568.1:p.Glu1302Ter nonsense NM_001407640.1:c.3904G>T NP_001394569.1:p.Glu1302Ter nonsense NM_001407641.1:c.3904G>T NP_001394570.1:p.Glu1302Ter nonsense NM_001407642.1:c.3904G>T NP_001394571.1:p.Glu1302Ter nonsense NM_001407644.1:c.3901G>T NP_001394573.1:p.Glu1301Ter nonsense NM_001407645.1:c.3901G>T NP_001394574.1:p.Glu1301Ter nonsense NM_001407646.1:c.3895G>T NP_001394575.1:p.Glu1299Ter nonsense NM_001407647.1:c.3895G>T NP_001394576.1:p.Glu1299Ter nonsense NM_001407648.1:c.3781G>T NP_001394577.1:p.Glu1261Ter nonsense NM_001407649.1:c.3778G>T NP_001394578.1:p.Glu1260Ter nonsense NM_001407652.1:c.3904G>T NP_001394581.1:p.Glu1302Ter nonsense NM_001407653.1:c.3826G>T NP_001394582.1:p.Glu1276Ter nonsense NM_001407654.1:c.3826G>T NP_001394583.1:p.Glu1276Ter nonsense NM_001407655.1:c.3826G>T NP_001394584.1:p.Glu1276Ter nonsense NM_001407656.1:c.3826G>T NP_001394585.1:p.Glu1276Ter nonsense NM_001407657.1:c.3826G>T NP_001394586.1:p.Glu1276Ter nonsense NM_001407658.1:c.3826G>T NP_001394587.1:p.Glu1276Ter nonsense NM_001407659.1:c.3823G>T NP_001394588.1:p.Glu1275Ter nonsense NM_001407660.1:c.3823G>T NP_001394589.1:p.Glu1275Ter nonsense NM_001407661.1:c.3823G>T NP_001394590.1:p.Glu1275Ter nonsense NM_001407662.1:c.3823G>T NP_001394591.1:p.Glu1275Ter nonsense NM_001407663.1:c.3826G>T NP_001394592.1:p.Glu1276Ter nonsense NM_001407664.1:c.3781G>T NP_001394593.1:p.Glu1261Ter nonsense NM_001407665.1:c.3781G>T NP_001394594.1:p.Glu1261Ter nonsense NM_001407666.1:c.3781G>T NP_001394595.1:p.Glu1261Ter nonsense NM_001407667.1:c.3781G>T NP_001394596.1:p.Glu1261Ter nonsense NM_001407668.1:c.3781G>T NP_001394597.1:p.Glu1261Ter nonsense NM_001407669.1:c.3781G>T NP_001394598.1:p.Glu1261Ter nonsense NM_001407670.1:c.3778G>T NP_001394599.1:p.Glu1260Ter nonsense NM_001407671.1:c.3778G>T NP_001394600.1:p.Glu1260Ter nonsense NM_001407672.1:c.3778G>T NP_001394601.1:p.Glu1260Ter nonsense NM_001407673.1:c.3778G>T NP_001394602.1:p.Glu1260Ter nonsense NM_001407674.1:c.3781G>T NP_001394603.1:p.Glu1261Ter nonsense NM_001407675.1:c.3781G>T NP_001394604.1:p.Glu1261Ter nonsense NM_001407676.1:c.3781G>T NP_001394605.1:p.Glu1261Ter nonsense NM_001407677.1:c.3781G>T NP_001394606.1:p.Glu1261Ter nonsense NM_001407678.1:c.3781G>T NP_001394607.1:p.Glu1261Ter nonsense NM_001407679.1:c.3781G>T NP_001394608.1:p.Glu1261Ter nonsense NM_001407680.1:c.3781G>T NP_001394609.1:p.Glu1261Ter nonsense NM_001407681.1:c.3781G>T NP_001394610.1:p.Glu1261Ter nonsense NM_001407682.1:c.3781G>T NP_001394611.1:p.Glu1261Ter nonsense NM_001407683.1:c.3781G>T NP_001394612.1:p.Glu1261Ter nonsense NM_001407684.1:c.3904G>T NP_001394613.1:p.Glu1302Ter nonsense NM_001407685.1:c.3778G>T NP_001394614.1:p.Glu1260Ter nonsense NM_001407686.1:c.3778G>T NP_001394615.1:p.Glu1260Ter nonsense NM_001407687.1:c.3778G>T NP_001394616.1:p.Glu1260Ter nonsense NM_001407688.1:c.3778G>T NP_001394617.1:p.Glu1260Ter nonsense NM_001407689.1:c.3778G>T NP_001394618.1:p.Glu1260Ter nonsense NM_001407690.1:c.3778G>T NP_001394619.1:p.Glu1260Ter nonsense NM_001407691.1:c.3778G>T NP_001394620.1:p.Glu1260Ter nonsense NM_001407692.1:c.3763G>T NP_001394621.1:p.Glu1255Ter nonsense NM_001407694.1:c.3763G>T NP_001394623.1:p.Glu1255Ter nonsense NM_001407695.1:c.3763G>T NP_001394624.1:p.Glu1255Ter nonsense NM_001407696.1:c.3763G>T NP_001394625.1:p.Glu1255Ter nonsense NM_001407697.1:c.3763G>T NP_001394626.1:p.Glu1255Ter nonsense NM_001407698.1:c.3763G>T NP_001394627.1:p.Glu1255Ter nonsense NM_001407724.1:c.3763G>T NP_001394653.1:p.Glu1255Ter nonsense NM_001407725.1:c.3763G>T NP_001394654.1:p.Glu1255Ter nonsense NM_001407726.1:c.3763G>T NP_001394655.1:p.Glu1255Ter nonsense NM_001407727.1:c.3763G>T NP_001394656.1:p.Glu1255Ter nonsense NM_001407728.1:c.3763G>T NP_001394657.1:p.Glu1255Ter nonsense NM_001407729.1:c.3763G>T NP_001394658.1:p.Glu1255Ter nonsense NM_001407730.1:c.3763G>T NP_001394659.1:p.Glu1255Ter nonsense NM_001407731.1:c.3763G>T NP_001394660.1:p.Glu1255Ter nonsense NM_001407732.1:c.3763G>T NP_001394661.1:p.Glu1255Ter nonsense NM_001407733.1:c.3763G>T NP_001394662.1:p.Glu1255Ter nonsense NM_001407734.1:c.3763G>T NP_001394663.1:p.Glu1255Ter nonsense NM_001407735.1:c.3763G>T NP_001394664.1:p.Glu1255Ter nonsense NM_001407736.1:c.3763G>T NP_001394665.1:p.Glu1255Ter nonsense NM_001407737.1:c.3763G>T NP_001394666.1:p.Glu1255Ter nonsense NM_001407738.1:c.3763G>T NP_001394667.1:p.Glu1255Ter nonsense NM_001407739.1:c.3763G>T NP_001394668.1:p.Glu1255Ter nonsense NM_001407740.1:c.3760G>T NP_001394669.1:p.Glu1254Ter nonsense NM_001407741.1:c.3760G>T NP_001394670.1:p.Glu1254Ter nonsense NM_001407742.1:c.3760G>T NP_001394671.1:p.Glu1254Ter nonsense NM_001407743.1:c.3760G>T NP_001394672.1:p.Glu1254Ter nonsense NM_001407744.1:c.3760G>T NP_001394673.1:p.Glu1254Ter nonsense NM_001407745.1:c.3760G>T NP_001394674.1:p.Glu1254Ter nonsense NM_001407746.1:c.3760G>T NP_001394675.1:p.Glu1254Ter nonsense NM_001407747.1:c.3760G>T NP_001394676.1:p.Glu1254Ter nonsense NM_001407748.1:c.3760G>T NP_001394677.1:p.Glu1254Ter nonsense NM_001407749.1:c.3760G>T NP_001394678.1:p.Glu1254Ter nonsense NM_001407750.1:c.3763G>T NP_001394679.1:p.Glu1255Ter nonsense NM_001407751.1:c.3763G>T NP_001394680.1:p.Glu1255Ter nonsense NM_001407752.1:c.3763G>T NP_001394681.1:p.Glu1255Ter nonsense NM_001407838.1:c.3760G>T NP_001394767.1:p.Glu1254Ter nonsense NM_001407839.1:c.3760G>T NP_001394768.1:p.Glu1254Ter nonsense NM_001407841.1:c.3760G>T NP_001394770.1:p.Glu1254Ter nonsense NM_001407842.1:c.3760G>T NP_001394771.1:p.Glu1254Ter nonsense NM_001407843.1:c.3760G>T NP_001394772.1:p.Glu1254Ter nonsense NM_001407844.1:c.3760G>T NP_001394773.1:p.Glu1254Ter nonsense NM_001407845.1:c.3760G>T NP_001394774.1:p.Glu1254Ter nonsense NM_001407846.1:c.3760G>T NP_001394775.1:p.Glu1254Ter nonsense NM_001407847.1:c.3760G>T NP_001394776.1:p.Glu1254Ter nonsense NM_001407848.1:c.3760G>T NP_001394777.1:p.Glu1254Ter nonsense NM_001407849.1:c.3760G>T NP_001394778.1:p.Glu1254Ter nonsense NM_001407850.1:c.3763G>T NP_001394779.1:p.Glu1255Ter nonsense NM_001407851.1:c.3763G>T NP_001394780.1:p.Glu1255Ter nonsense NM_001407852.1:c.3763G>T NP_001394781.1:p.Glu1255Ter nonsense NM_001407853.1:c.3691G>T NP_001394782.1:p.Glu1231Ter nonsense NM_001407854.1:c.3904G>T NP_001394783.1:p.Glu1302Ter nonsense NM_001407858.1:c.3904G>T NP_001394787.1:p.Glu1302Ter nonsense NM_001407859.1:c.3904G>T NP_001394788.1:p.Glu1302Ter nonsense NM_001407860.1:c.3901G>T NP_001394789.1:p.Glu1301Ter nonsense NM_001407861.1:c.3901G>T NP_001394790.1:p.Glu1301Ter nonsense NM_001407862.1:c.3703G>T NP_001394791.1:p.Glu1235Ter nonsense NM_001407863.1:c.3781G>T NP_001394792.1:p.Glu1261Ter nonsense NM_001407874.1:c.3700G>T NP_001394803.1:p.Glu1234Ter nonsense NM_001407875.1:c.3700G>T NP_001394804.1:p.Glu1234Ter nonsense NM_001407879.1:c.3694G>T NP_001394808.1:p.Glu1232Ter nonsense NM_001407881.1:c.3694G>T NP_001394810.1:p.Glu1232Ter nonsense NM_001407882.1:c.3694G>T NP_001394811.1:p.Glu1232Ter nonsense NM_001407884.1:c.3694G>T NP_001394813.1:p.Glu1232Ter nonsense NM_001407885.1:c.3694G>T NP_001394814.1:p.Glu1232Ter nonsense NM_001407886.1:c.3694G>T NP_001394815.1:p.Glu1232Ter nonsense NM_001407887.1:c.3694G>T NP_001394816.1:p.Glu1232Ter nonsense NM_001407889.1:c.3694G>T NP_001394818.1:p.Glu1232Ter nonsense NM_001407894.1:c.3691G>T NP_001394823.1:p.Glu1231Ter nonsense NM_001407895.1:c.3691G>T NP_001394824.1:p.Glu1231Ter nonsense NM_001407896.1:c.3691G>T NP_001394825.1:p.Glu1231Ter nonsense NM_001407897.1:c.3691G>T NP_001394826.1:p.Glu1231Ter nonsense NM_001407898.1:c.3691G>T NP_001394827.1:p.Glu1231Ter nonsense NM_001407899.1:c.3691G>T NP_001394828.1:p.Glu1231Ter nonsense NM_001407900.1:c.3694G>T NP_001394829.1:p.Glu1232Ter nonsense NM_001407902.1:c.3694G>T NP_001394831.1:p.Glu1232Ter nonsense NM_001407904.1:c.3694G>T NP_001394833.1:p.Glu1232Ter nonsense NM_001407906.1:c.3694G>T NP_001394835.1:p.Glu1232Ter nonsense NM_001407907.1:c.3694G>T NP_001394836.1:p.Glu1232Ter nonsense NM_001407908.1:c.3694G>T NP_001394837.1:p.Glu1232Ter nonsense NM_001407909.1:c.3694G>T NP_001394838.1:p.Glu1232Ter nonsense NM_001407910.1:c.3694G>T NP_001394839.1:p.Glu1232Ter nonsense NM_001407915.1:c.3691G>T NP_001394844.1:p.Glu1231Ter nonsense NM_001407916.1:c.3691G>T NP_001394845.1:p.Glu1231Ter nonsense NM_001407917.1:c.3691G>T NP_001394846.1:p.Glu1231Ter nonsense NM_001407918.1:c.3691G>T NP_001394847.1:p.Glu1231Ter nonsense NM_001407919.1:c.3781G>T NP_001394848.1:p.Glu1261Ter nonsense NM_001407920.1:c.3640G>T NP_001394849.1:p.Glu1214Ter nonsense NM_001407921.1:c.3640G>T NP_001394850.1:p.Glu1214Ter nonsense NM_001407922.1:c.3640G>T NP_001394851.1:p.Glu1214Ter nonsense NM_001407923.1:c.3640G>T NP_001394852.1:p.Glu1214Ter nonsense NM_001407924.1:c.3640G>T NP_001394853.1:p.Glu1214Ter nonsense NM_001407925.1:c.3640G>T NP_001394854.1:p.Glu1214Ter nonsense NM_001407926.1:c.3640G>T NP_001394855.1:p.Glu1214Ter nonsense NM_001407927.1:c.3640G>T NP_001394856.1:p.Glu1214Ter nonsense NM_001407928.1:c.3640G>T NP_001394857.1:p.Glu1214Ter nonsense NM_001407929.1:c.3640G>T NP_001394858.1:p.Glu1214Ter nonsense NM_001407930.1:c.3637G>T NP_001394859.1:p.Glu1213Ter nonsense NM_001407931.1:c.3637G>T NP_001394860.1:p.Glu1213Ter nonsense NM_001407932.1:c.3637G>T NP_001394861.1:p.Glu1213Ter nonsense NM_001407933.1:c.3640G>T NP_001394862.1:p.Glu1214Ter nonsense NM_001407934.1:c.3637G>T NP_001394863.1:p.Glu1213Ter nonsense NM_001407935.1:c.3640G>T NP_001394864.1:p.Glu1214Ter nonsense NM_001407936.1:c.3637G>T NP_001394865.1:p.Glu1213Ter nonsense NM_001407937.1:c.3781G>T NP_001394866.1:p.Glu1261Ter nonsense NM_001407938.1:c.3781G>T NP_001394867.1:p.Glu1261Ter nonsense NM_001407939.1:c.3781G>T NP_001394868.1:p.Glu1261Ter nonsense NM_001407940.1:c.3778G>T NP_001394869.1:p.Glu1260Ter nonsense NM_001407941.1:c.3778G>T NP_001394870.1:p.Glu1260Ter nonsense NM_001407942.1:c.3763G>T NP_001394871.1:p.Glu1255Ter nonsense NM_001407943.1:c.3760G>T NP_001394872.1:p.Glu1254Ter nonsense NM_001407944.1:c.3763G>T NP_001394873.1:p.Glu1255Ter nonsense NM_001407945.1:c.3763G>T NP_001394874.1:p.Glu1255Ter nonsense NM_001407946.1:c.3571G>T NP_001394875.1:p.Glu1191Ter nonsense NM_001407947.1:c.3571G>T NP_001394876.1:p.Glu1191Ter nonsense NM_001407948.1:c.3571G>T NP_001394877.1:p.Glu1191Ter nonsense NM_001407949.1:c.3571G>T NP_001394878.1:p.Glu1191Ter nonsense NM_001407950.1:c.3571G>T NP_001394879.1:p.Glu1191Ter nonsense NM_001407951.1:c.3571G>T NP_001394880.1:p.Glu1191Ter nonsense NM_001407952.1:c.3571G>T NP_001394881.1:p.Glu1191Ter nonsense NM_001407953.1:c.3571G>T NP_001394882.1:p.Glu1191Ter nonsense NM_001407954.1:c.3568G>T NP_001394883.1:p.Glu1190Ter nonsense NM_001407955.1:c.3568G>T NP_001394884.1:p.Glu1190Ter nonsense NM_001407956.1:c.3568G>T NP_001394885.1:p.Glu1190Ter nonsense NM_001407957.1:c.3571G>T NP_001394886.1:p.Glu1191Ter nonsense NM_001407958.1:c.3568G>T NP_001394887.1:p.Glu1190Ter nonsense NM_001407959.1:c.3523G>T NP_001394888.1:p.Glu1175Ter nonsense NM_001407960.1:c.3523G>T NP_001394889.1:p.Glu1175Ter nonsense NM_001407962.1:c.3520G>T NP_001394891.1:p.Glu1174Ter nonsense NM_001407963.1:c.3523G>T NP_001394892.1:p.Glu1175Ter nonsense NM_001407964.1:c.3760G>T NP_001394893.1:p.Glu1254Ter nonsense NM_001407965.1:c.3400G>T NP_001394894.1:p.Glu1134Ter nonsense NM_001407966.1:c.3016G>T NP_001394895.1:p.Glu1006Ter nonsense NM_001407967.1:c.3016G>T NP_001394896.1:p.Glu1006Ter nonsense NM_001407968.1:c.1300G>T NP_001394897.1:p.Glu434Ter nonsense NM_001407969.1:c.1300G>T NP_001394898.1:p.Glu434Ter nonsense NM_001407970.1:c.788-595G>T intron variant NM_001407971.1:c.788-595G>T intron variant NM_001407972.1:c.785-595G>T intron variant NM_001407973.1:c.788-595G>T intron variant NM_001407974.1:c.788-595G>T intron variant NM_001407975.1:c.788-595G>T intron variant NM_001407976.1:c.788-595G>T intron variant NM_001407977.1:c.788-595G>T intron variant NM_001407978.1:c.788-595G>T intron variant NM_001407979.1:c.788-595G>T intron variant NM_001407980.1:c.788-595G>T intron variant NM_001407981.1:c.788-595G>T intron variant NM_001407982.1:c.788-595G>T intron variant NM_001407983.1:c.788-595G>T intron variant NM_001407984.1:c.785-595G>T intron variant NM_001407985.1:c.785-595G>T intron variant NM_001407986.1:c.785-595G>T intron variant NM_001407990.1:c.788-595G>T intron variant NM_001407991.1:c.785-595G>T intron variant NM_001407992.1:c.785-595G>T intron variant NM_001407993.1:c.788-595G>T intron variant NM_001408392.1:c.785-595G>T intron variant NM_001408396.1:c.785-595G>T intron variant NM_001408397.1:c.785-595G>T intron variant NM_001408398.1:c.785-595G>T intron variant NM_001408399.1:c.785-595G>T intron variant NM_001408400.1:c.785-595G>T intron variant NM_001408401.1:c.785-595G>T intron variant NM_001408402.1:c.785-595G>T intron variant NM_001408403.1:c.788-595G>T intron variant NM_001408404.1:c.788-595G>T intron variant NM_001408406.1:c.791-604G>T intron variant NM_001408407.1:c.785-595G>T intron variant NM_001408408.1:c.779-595G>T intron variant NM_001408409.1:c.710-595G>T intron variant NM_001408410.1:c.647-595G>T intron variant NM_001408411.1:c.710-595G>T intron variant NM_001408412.1:c.710-595G>T intron variant NM_001408413.1:c.707-595G>T intron variant NM_001408414.1:c.710-595G>T intron variant NM_001408415.1:c.710-595G>T intron variant NM_001408416.1:c.707-595G>T intron variant NM_001408418.1:c.671-595G>T intron variant NM_001408419.1:c.671-595G>T intron variant NM_001408420.1:c.671-595G>T intron variant NM_001408421.1:c.668-595G>T intron variant NM_001408422.1:c.671-595G>T intron variant NM_001408423.1:c.671-595G>T intron variant NM_001408424.1:c.668-595G>T intron variant NM_001408425.1:c.665-595G>T intron variant NM_001408426.1:c.665-595G>T intron variant NM_001408427.1:c.665-595G>T intron variant NM_001408428.1:c.665-595G>T intron variant NM_001408429.1:c.665-595G>T intron variant NM_001408430.1:c.665-595G>T intron variant NM_001408431.1:c.668-595G>T intron variant NM_001408432.1:c.662-595G>T intron variant NM_001408433.1:c.662-595G>T intron variant NM_001408434.1:c.662-595G>T intron variant NM_001408435.1:c.662-595G>T intron variant NM_001408436.1:c.665-595G>T intron variant NM_001408437.1:c.665-595G>T intron variant NM_001408438.1:c.665-595G>T intron variant NM_001408439.1:c.665-595G>T intron variant NM_001408440.1:c.665-595G>T intron variant NM_001408441.1:c.665-595G>T intron variant NM_001408442.1:c.665-595G>T intron variant NM_001408443.1:c.665-595G>T intron variant NM_001408444.1:c.665-595G>T intron variant NM_001408445.1:c.662-595G>T intron variant NM_001408446.1:c.662-595G>T intron variant NM_001408447.1:c.662-595G>T intron variant NM_001408448.1:c.662-595G>T intron variant NM_001408450.1:c.662-595G>T intron variant NM_001408451.1:c.653-595G>T intron variant NM_001408452.1:c.647-595G>T intron variant NM_001408453.1:c.647-595G>T intron variant NM_001408454.1:c.647-595G>T intron variant NM_001408455.1:c.647-595G>T intron variant NM_001408456.1:c.647-595G>T intron variant NM_001408457.1:c.647-595G>T intron variant NM_001408458.1:c.647-595G>T intron variant NM_001408459.1:c.647-595G>T intron variant NM_001408460.1:c.647-595G>T intron variant NM_001408461.1:c.647-595G>T intron variant NM_001408462.1:c.644-595G>T intron variant NM_001408463.1:c.644-595G>T intron variant NM_001408464.1:c.644-595G>T intron variant NM_001408465.1:c.644-595G>T intron variant NM_001408466.1:c.647-595G>T intron variant NM_001408467.1:c.647-595G>T intron variant NM_001408468.1:c.644-595G>T intron variant NM_001408469.1:c.647-595G>T intron variant NM_001408470.1:c.644-595G>T intron variant NM_001408472.1:c.788-595G>T intron variant NM_001408473.1:c.785-595G>T intron variant NM_001408474.1:c.587-595G>T intron variant NM_001408475.1:c.584-595G>T intron variant NM_001408476.1:c.587-595G>T intron variant NM_001408478.1:c.578-595G>T intron variant NM_001408479.1:c.578-595G>T intron variant NM_001408480.1:c.578-595G>T intron variant NM_001408481.1:c.578-595G>T intron variant NM_001408482.1:c.578-595G>T intron variant NM_001408483.1:c.578-595G>T intron variant NM_001408484.1:c.578-595G>T intron variant NM_001408485.1:c.578-595G>T intron variant NM_001408489.1:c.578-595G>T intron variant NM_001408490.1:c.575-595G>T intron variant NM_001408491.1:c.575-595G>T intron variant NM_001408492.1:c.578-595G>T intron variant NM_001408493.1:c.575-595G>T intron variant NM_001408494.1:c.548-595G>T intron variant NM_001408495.1:c.545-595G>T intron variant NM_001408496.1:c.524-595G>T intron variant NM_001408497.1:c.524-595G>T intron variant NM_001408498.1:c.524-595G>T intron variant NM_001408499.1:c.524-595G>T intron variant NM_001408500.1:c.524-595G>T intron variant NM_001408501.1:c.524-595G>T intron variant NM_001408502.1:c.455-595G>T intron variant NM_001408503.1:c.521-595G>T intron variant NM_001408504.1:c.521-595G>T intron variant NM_001408505.1:c.521-595G>T intron variant NM_001408506.1:c.461-595G>T intron variant NM_001408507.1:c.461-595G>T intron variant NM_001408508.1:c.452-595G>T intron variant NM_001408509.1:c.452-595G>T intron variant NM_001408510.1:c.407-595G>T intron variant NM_001408511.1:c.404-595G>T intron variant NM_001408512.1:c.284-595G>T intron variant NM_001408513.1:c.578-595G>T intron variant NM_001408514.1:c.578-595G>T intron variant NM_007297.4:c.3763G>T NP_009228.2:p.Glu1255Ter nonsense NM_007298.4:c.788-595G>T intron variant NM_007299.4:c.788-595G>T intron variant NM_007300.4:c.3904G>T NP_009231.2:p.Glu1302Ter nonsense NR_027676.1:n.4040G>T NC_000017.11:g.43091627C>A NC_000017.10:g.41243644C>A NG_005905.2:g.126357G>T NG_087068.1:g.609C>A LRG_292:g.126357G>T LRG_292t1:c.3904G>T LRG_292p1:p.Glu1302Ter U14680.1:n.4023G>T - Protein change
- E1302*, E1255*, E1175*, E1190*, E1231*, E1301*, E1006*, E1174*, E1214*, E1232*, E1261*, E1299*, E434*, E1134*, E1191*, E1254*, E1260*, E1275*, E1213*, E1234*, E1235*, E1276*
- Other names
-
4023G>T
- Canonical SPDI
- NC_000017.11:43091626:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13040 | 14846 | |
| LOC126862571 | - | - | - | GRCh38 | - | 1651 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (5) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000083199.16 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2024 | RCV000484534.17 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Nov 24, 2023 | RCV000496224.21 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 11, 2021 | RCV000569716.16 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Sep 08, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000300040.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
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Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000325782.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Aug 09, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848205.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Glu1302X variant in BRCA1 has been reported in at least 3 individuals with breast cancer, and segregated with disease in one affected relative (Casadei … (more)
The p.Glu1302X variant in BRCA1 has been reported in at least 3 individuals with breast cancer, and segregated with disease in one affected relative (Casadei 2001, Nielsen 2016, Ramus 2017). In addition, this variant was classified as Pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300040.2) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1302 which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovariant cancer. In summary, this variant meets criteria to be classified as pathogenic for hereditary breast and ovarian cancer in an autosomal dominant manner based case reports, absence from controls and predicted impact on protein. ACMG/AMP Criteria applied: PM2,PVS1, PS4_Supporting. (less)
|
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Pathogenic
(May 27, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045964.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM2_supporting; PM5_PTC_Strong
|
|
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Pathogenic
(Jul 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550985.6
First in ClinVar: Jul 30, 2022 Last updated: Aug 04, 2024 |
|
|
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Pathogenic
(May 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199723.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Jan 15, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000909286.3
First in ClinVar: May 20, 2019 Last updated: Jan 15, 2022 |
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Aug 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000567704.5
First in ClinVar: Apr 27, 2017 Last updated: Aug 13, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with personal or family history of breast or ovarian cancer (Casadei et al., 2001; Judkins et al., 2005; Ramus et al., 2007; Nielsen et al., 2016); Also known as 4023G>T; This variant is associated with the following publications: (PMID: 19826428, 25525159, 17688236, 16267036, 26833046, 22762150, 32854451, 29446198, 11556835, 15781624, 30128899, 33403015, 33471991, 31209999, 31853058, 29884841, 32377563, 37460658, 32380732) (less)
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Pathogenic
(Nov 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001586045.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu1302*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu1302*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 17688236). ClinVar contains an entry for this variant (Variation ID: 55045). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 11, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000665797.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The p.E1302* pathogenic mutation (also known as c.3904G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at … (more)
The p.E1302* pathogenic mutation (also known as c.3904G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3904. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This alteration has been reported in multiple individuals diagnosed with breast and/or ovarian cancer (Ramus SJ et al. Hum. Mutat. 2007 Dec; 28(12):1207-15; Nielsen HR et al. Fam. Cancer 2016 Feb; Marchetti C et al. Ann Surg Oncol, 2018 Nov;25:3701-3708; Fanale D et al. Cancers (Basel), 2020 Aug;12:; Incorvaia L et al. Ther Adv Med Oncol, 2020 Dec;12:1758835920975326; Dorling et al. N Engl J Med. 2021 02;384:428-439). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Nov 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918798.3
First in ClinVar: Jun 02, 2019 Last updated: Jun 09, 2024 |
Comment:
Variant summary: BRCA1 c.3904G>T (p.Glu1302X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.3904G>T (p.Glu1302X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251170 control chromosomes. c.3904G>T has been reported in the literature in multiple individuals affected with or with family history of Hereditary Breast And Ovarian Cancer Syndrome (HBOC) (e.g. Judkins_2005, Lecarpentier_2012, Ramus_2007, Sirchia_2005, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (e.g. Sirchia_2005). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144914.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Italian
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
|
|
|
Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587357.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
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Pathogenic
(May 01, 2012)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000115273.4
First in ClinVar: Feb 06, 2014 Last updated: Sep 27, 2014 |
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Comment:
Comment:
The p.Glu1302X variant in BRCA1 has been reported in at least 3 individuals with breast cancer, and segregated with disease in one affected relative (Casadei 2001, Nielsen 2016, Ramus 2017). In addition, this variant was classified as Pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300040.2) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1302 which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovariant cancer. In summary, this variant meets criteria to be classified as pathogenic for hereditary breast and ovarian cancer in an autosomal dominant manner based case reports, absence from controls and predicted impact on protein. ACMG/AMP Criteria applied: PM2,PVS1, PS4_Supporting.
Comment:
PVS1; PM2_supporting; PM5_PTC_Strong
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with personal or family history of breast or ovarian cancer (Casadei et al., 2001; Judkins et al., 2005; Ramus et al., 2007; Nielsen et al., 2016); Also known as 4023G>T; This variant is associated with the following publications: (PMID: 19826428, 25525159, 17688236, 16267036, 26833046, 22762150, 32854451, 29446198, 11556835, 15781624, 30128899, 33403015, 33471991, 31209999, 31853058, 29884841, 32377563, 37460658, 32380732)
Comment:
This sequence change creates a premature translational stop signal (p.Glu1302*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 17688236). ClinVar contains an entry for this variant (Variation ID: 55045). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.E1302* pathogenic mutation (also known as c.3904G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3904. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This alteration has been reported in multiple individuals diagnosed with breast and/or ovarian cancer (Ramus SJ et al. Hum. Mutat. 2007 Dec; 28(12):1207-15; Nielsen HR et al. Fam. Cancer 2016 Feb; Marchetti C et al. Ann Surg Oncol, 2018 Nov;25:3701-3708; Fanale D et al. Cancers (Basel), 2020 Aug;12:; Incorvaia L et al. Ther Adv Med Oncol, 2020 Dec;12:1758835920975326; Dorling et al. N Engl J Med. 2021 02;384:428-439). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Variant summary: BRCA1 c.3904G>T (p.Glu1302X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251170 control chromosomes. c.3904G>T has been reported in the literature in multiple individuals affected with or with family history of Hereditary Breast And Ovarian Cancer Syndrome (HBOC) (e.g. Judkins_2005, Lecarpentier_2012, Ramus_2007, Sirchia_2005, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (e.g. Sirchia_2005). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
The p.Glu1302X variant in BRCA1 has been reported in at least 3 individuals with breast cancer, and segregated with disease in one affected relative (Casadei 2001, Nielsen 2016, Ramus 2017). In addition, this variant was classified as Pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300040.2) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1302 which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovariant cancer. In summary, this variant meets criteria to be classified as pathogenic for hereditary breast and ovarian cancer in an autosomal dominant manner based case reports, absence from controls and predicted impact on protein. ACMG/AMP Criteria applied: PM2,PVS1, PS4_Supporting.
Comment:
PVS1; PM2_supporting; PM5_PTC_Strong
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with personal or family history of breast or ovarian cancer (Casadei et al., 2001; Judkins et al., 2005; Ramus et al., 2007; Nielsen et al., 2016); Also known as 4023G>T; This variant is associated with the following publications: (PMID: 19826428, 25525159, 17688236, 16267036, 26833046, 22762150, 32854451, 29446198, 11556835, 15781624, 30128899, 33403015, 33471991, 31209999, 31853058, 29884841, 32377563, 37460658, 32380732)
Comment:
This sequence change creates a premature translational stop signal (p.Glu1302*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 17688236). ClinVar contains an entry for this variant (Variation ID: 55045). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.E1302* pathogenic mutation (also known as c.3904G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3904. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This alteration has been reported in multiple individuals diagnosed with breast and/or ovarian cancer (Ramus SJ et al. Hum. Mutat. 2007 Dec; 28(12):1207-15; Nielsen HR et al. Fam. Cancer 2016 Feb; Marchetti C et al. Ann Surg Oncol, 2018 Nov;25:3701-3708; Fanale D et al. Cancers (Basel), 2020 Aug;12:; Incorvaia L et al. Ther Adv Med Oncol, 2020 Dec;12:1758835920975326; Dorling et al. N Engl J Med. 2021 02;384:428-439). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Variant summary: BRCA1 c.3904G>T (p.Glu1302X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251170 control chromosomes. c.3904G>T has been reported in the literature in multiple individuals affected with or with family history of Hereditary Breast And Ovarian Cancer Syndrome (HBOC) (e.g. Judkins_2005, Lecarpentier_2012, Ramus_2007, Sirchia_2005, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (e.g. Sirchia_2005). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype-phenotype correlation in a cohort of 531 patients. | Incorvaia L | Therapeutic advances in medical oncology | 2020 | PMID: 33403015 |
| Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2. | Fanale D | Cancers | 2020 | PMID: 32854451 |
| BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study. | Marchetti C | Annals of surgical oncology | 2018 | PMID: 30128899 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population. | Nielsen HR | Familial cancer | 2016 | PMID: 26833046 |
| Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO). | Lecarpentier J | Breast cancer research : BCR | 2012 | PMID: 22762150 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer. | Ramus SJ | Human mutation | 2007 | PMID: 17688236 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| Loss of the inactive X chromosome and replication of the active X in BRCA1-defective and wild-type breast cancer cells. | Sirchia SM | Cancer research | 2005 | PMID: 15781624 |
| Detection of germline BRCA1 mutations by Multiple-Dye Cleavase Fragment Length Polymorphism (MD-CFLP) method. | Casadei S | British journal of cancer | 2001 | PMID: 11556835 |
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Text-mined citations for rs80357461 ...
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Record last updated Nov 03, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.