In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55036). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 30254663). This variant is present in population databases (rs80357213, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1293 of the BRCA1 protein (p.Ala1293Val).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3878C>T (p.Ala1293Val)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(7)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(1)
Uncertain significance(2); Likely benign(1)
7
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.3878C>T (p.Ala1293Val)
Variation ID: 55036 Accession: VCV000055036.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091653 (GRCh38) [ NCBI UCSC ] 17: 41243670 (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 May 1, 2024 Aug 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3878C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1293Val missense NM_001407571.1:c.3665C>T NP_001394500.1:p.Ala1222Val missense NM_001407581.1:c.3878C>T NP_001394510.1:p.Ala1293Val missense NM_001407582.1:c.3878C>T NP_001394511.1:p.Ala1293Val missense NM_001407583.1:c.3878C>T NP_001394512.1:p.Ala1293Val missense NM_001407585.1:c.3878C>T NP_001394514.1:p.Ala1293Val missense NM_001407587.1:c.3875C>T NP_001394516.1:p.Ala1292Val missense NM_001407590.1:c.3875C>T NP_001394519.1:p.Ala1292Val missense NM_001407591.1:c.3875C>T NP_001394520.1:p.Ala1292Val missense NM_001407593.1:c.3878C>T NP_001394522.1:p.Ala1293Val missense NM_001407594.1:c.3878C>T NP_001394523.1:p.Ala1293Val missense NM_001407596.1:c.3878C>T NP_001394525.1:p.Ala1293Val missense NM_001407597.1:c.3878C>T NP_001394526.1:p.Ala1293Val missense NM_001407598.1:c.3878C>T NP_001394527.1:p.Ala1293Val missense NM_001407602.1:c.3878C>T NP_001394531.1:p.Ala1293Val missense NM_001407603.1:c.3878C>T NP_001394532.1:p.Ala1293Val missense NM_001407605.1:c.3878C>T NP_001394534.1:p.Ala1293Val missense NM_001407610.1:c.3875C>T NP_001394539.1:p.Ala1292Val missense NM_001407611.1:c.3875C>T NP_001394540.1:p.Ala1292Val missense NM_001407612.1:c.3875C>T NP_001394541.1:p.Ala1292Val missense NM_001407613.1:c.3875C>T NP_001394542.1:p.Ala1292Val missense NM_001407614.1:c.3875C>T NP_001394543.1:p.Ala1292Val missense NM_001407615.1:c.3875C>T NP_001394544.1:p.Ala1292Val missense NM_001407616.1:c.3878C>T NP_001394545.1:p.Ala1293Val missense NM_001407617.1:c.3878C>T NP_001394546.1:p.Ala1293Val missense NM_001407618.1:c.3878C>T NP_001394547.1:p.Ala1293Val missense NM_001407619.1:c.3878C>T NP_001394548.1:p.Ala1293Val missense NM_001407620.1:c.3878C>T NP_001394549.1:p.Ala1293Val missense NM_001407621.1:c.3878C>T NP_001394550.1:p.Ala1293Val missense NM_001407622.1:c.3878C>T NP_001394551.1:p.Ala1293Val missense NM_001407623.1:c.3878C>T NP_001394552.1:p.Ala1293Val missense NM_001407624.1:c.3878C>T NP_001394553.1:p.Ala1293Val missense NM_001407625.1:c.3878C>T NP_001394554.1:p.Ala1293Val missense NM_001407626.1:c.3878C>T NP_001394555.1:p.Ala1293Val missense NM_001407627.1:c.3875C>T NP_001394556.1:p.Ala1292Val missense NM_001407628.1:c.3875C>T NP_001394557.1:p.Ala1292Val missense NM_001407629.1:c.3875C>T NP_001394558.1:p.Ala1292Val missense NM_001407630.1:c.3875C>T NP_001394559.1:p.Ala1292Val missense NM_001407631.1:c.3875C>T NP_001394560.1:p.Ala1292Val missense NM_001407632.1:c.3875C>T NP_001394561.1:p.Ala1292Val missense NM_001407633.1:c.3875C>T NP_001394562.1:p.Ala1292Val missense NM_001407634.1:c.3875C>T NP_001394563.1:p.Ala1292Val missense NM_001407635.1:c.3875C>T NP_001394564.1:p.Ala1292Val missense NM_001407636.1:c.3875C>T NP_001394565.1:p.Ala1292Val missense NM_001407637.1:c.3875C>T NP_001394566.1:p.Ala1292Val missense NM_001407638.1:c.3875C>T NP_001394567.1:p.Ala1292Val missense NM_001407639.1:c.3878C>T NP_001394568.1:p.Ala1293Val missense NM_001407640.1:c.3878C>T NP_001394569.1:p.Ala1293Val missense NM_001407641.1:c.3878C>T NP_001394570.1:p.Ala1293Val missense NM_001407642.1:c.3878C>T NP_001394571.1:p.Ala1293Val missense NM_001407644.1:c.3875C>T NP_001394573.1:p.Ala1292Val missense NM_001407645.1:c.3875C>T NP_001394574.1:p.Ala1292Val missense NM_001407646.1:c.3869C>T NP_001394575.1:p.Ala1290Val missense NM_001407647.1:c.3869C>T NP_001394576.1:p.Ala1290Val missense NM_001407648.1:c.3755C>T NP_001394577.1:p.Ala1252Val missense NM_001407649.1:c.3752C>T NP_001394578.1:p.Ala1251Val missense NM_001407652.1:c.3878C>T NP_001394581.1:p.Ala1293Val missense NM_001407653.1:c.3800C>T NP_001394582.1:p.Ala1267Val missense NM_001407654.1:c.3800C>T NP_001394583.1:p.Ala1267Val missense NM_001407655.1:c.3800C>T NP_001394584.1:p.Ala1267Val missense NM_001407656.1:c.3800C>T NP_001394585.1:p.Ala1267Val missense NM_001407657.1:c.3800C>T NP_001394586.1:p.Ala1267Val missense NM_001407658.1:c.3800C>T NP_001394587.1:p.Ala1267Val missense NM_001407659.1:c.3797C>T NP_001394588.1:p.Ala1266Val missense NM_001407660.1:c.3797C>T NP_001394589.1:p.Ala1266Val missense NM_001407661.1:c.3797C>T NP_001394590.1:p.Ala1266Val missense NM_001407662.1:c.3797C>T NP_001394591.1:p.Ala1266Val missense NM_001407663.1:c.3800C>T NP_001394592.1:p.Ala1267Val missense NM_001407664.1:c.3755C>T NP_001394593.1:p.Ala1252Val missense NM_001407665.1:c.3755C>T NP_001394594.1:p.Ala1252Val missense NM_001407666.1:c.3755C>T NP_001394595.1:p.Ala1252Val missense NM_001407667.1:c.3755C>T NP_001394596.1:p.Ala1252Val missense NM_001407668.1:c.3755C>T NP_001394597.1:p.Ala1252Val missense NM_001407669.1:c.3755C>T NP_001394598.1:p.Ala1252Val missense NM_001407670.1:c.3752C>T NP_001394599.1:p.Ala1251Val missense NM_001407671.1:c.3752C>T NP_001394600.1:p.Ala1251Val missense NM_001407672.1:c.3752C>T NP_001394601.1:p.Ala1251Val missense NM_001407673.1:c.3752C>T NP_001394602.1:p.Ala1251Val missense NM_001407674.1:c.3755C>T NP_001394603.1:p.Ala1252Val missense NM_001407675.1:c.3755C>T NP_001394604.1:p.Ala1252Val missense NM_001407676.1:c.3755C>T NP_001394605.1:p.Ala1252Val missense NM_001407677.1:c.3755C>T NP_001394606.1:p.Ala1252Val missense NM_001407678.1:c.3755C>T NP_001394607.1:p.Ala1252Val missense NM_001407679.1:c.3755C>T NP_001394608.1:p.Ala1252Val missense NM_001407680.1:c.3755C>T NP_001394609.1:p.Ala1252Val missense NM_001407681.1:c.3755C>T NP_001394610.1:p.Ala1252Val missense NM_001407682.1:c.3755C>T NP_001394611.1:p.Ala1252Val missense NM_001407683.1:c.3755C>T NP_001394612.1:p.Ala1252Val missense NM_001407684.1:c.3878C>T NP_001394613.1:p.Ala1293Val missense NM_001407685.1:c.3752C>T NP_001394614.1:p.Ala1251Val missense NM_001407686.1:c.3752C>T NP_001394615.1:p.Ala1251Val missense NM_001407687.1:c.3752C>T NP_001394616.1:p.Ala1251Val missense NM_001407688.1:c.3752C>T NP_001394617.1:p.Ala1251Val missense NM_001407689.1:c.3752C>T NP_001394618.1:p.Ala1251Val missense NM_001407690.1:c.3752C>T NP_001394619.1:p.Ala1251Val missense NM_001407691.1:c.3752C>T NP_001394620.1:p.Ala1251Val missense NM_001407692.1:c.3737C>T NP_001394621.1:p.Ala1246Val missense NM_001407694.1:c.3737C>T NP_001394623.1:p.Ala1246Val missense NM_001407695.1:c.3737C>T NP_001394624.1:p.Ala1246Val missense NM_001407696.1:c.3737C>T NP_001394625.1:p.Ala1246Val missense NM_001407697.1:c.3737C>T NP_001394626.1:p.Ala1246Val missense NM_001407698.1:c.3737C>T NP_001394627.1:p.Ala1246Val missense NM_001407724.1:c.3737C>T NP_001394653.1:p.Ala1246Val missense NM_001407725.1:c.3737C>T NP_001394654.1:p.Ala1246Val missense NM_001407726.1:c.3737C>T NP_001394655.1:p.Ala1246Val missense NM_001407727.1:c.3737C>T NP_001394656.1:p.Ala1246Val missense NM_001407728.1:c.3737C>T NP_001394657.1:p.Ala1246Val missense NM_001407729.1:c.3737C>T NP_001394658.1:p.Ala1246Val missense NM_001407730.1:c.3737C>T NP_001394659.1:p.Ala1246Val missense NM_001407731.1:c.3737C>T NP_001394660.1:p.Ala1246Val missense NM_001407732.1:c.3737C>T NP_001394661.1:p.Ala1246Val missense NM_001407733.1:c.3737C>T NP_001394662.1:p.Ala1246Val missense NM_001407734.1:c.3737C>T NP_001394663.1:p.Ala1246Val missense NM_001407735.1:c.3737C>T NP_001394664.1:p.Ala1246Val missense NM_001407736.1:c.3737C>T NP_001394665.1:p.Ala1246Val missense NM_001407737.1:c.3737C>T NP_001394666.1:p.Ala1246Val missense NM_001407738.1:c.3737C>T NP_001394667.1:p.Ala1246Val missense NM_001407739.1:c.3737C>T NP_001394668.1:p.Ala1246Val missense NM_001407740.1:c.3734C>T NP_001394669.1:p.Ala1245Val missense NM_001407741.1:c.3734C>T NP_001394670.1:p.Ala1245Val missense NM_001407742.1:c.3734C>T NP_001394671.1:p.Ala1245Val missense NM_001407743.1:c.3734C>T NP_001394672.1:p.Ala1245Val missense NM_001407744.1:c.3734C>T NP_001394673.1:p.Ala1245Val missense NM_001407745.1:c.3734C>T NP_001394674.1:p.Ala1245Val missense NM_001407746.1:c.3734C>T NP_001394675.1:p.Ala1245Val missense NM_001407747.1:c.3734C>T NP_001394676.1:p.Ala1245Val missense NM_001407748.1:c.3734C>T NP_001394677.1:p.Ala1245Val missense NM_001407749.1:c.3734C>T NP_001394678.1:p.Ala1245Val missense NM_001407750.1:c.3737C>T NP_001394679.1:p.Ala1246Val missense NM_001407751.1:c.3737C>T NP_001394680.1:p.Ala1246Val missense NM_001407752.1:c.3737C>T NP_001394681.1:p.Ala1246Val missense NM_001407838.1:c.3734C>T NP_001394767.1:p.Ala1245Val missense NM_001407839.1:c.3734C>T NP_001394768.1:p.Ala1245Val missense NM_001407841.1:c.3734C>T NP_001394770.1:p.Ala1245Val missense NM_001407842.1:c.3734C>T NP_001394771.1:p.Ala1245Val missense NM_001407843.1:c.3734C>T NP_001394772.1:p.Ala1245Val missense NM_001407844.1:c.3734C>T NP_001394773.1:p.Ala1245Val missense NM_001407845.1:c.3734C>T NP_001394774.1:p.Ala1245Val missense NM_001407846.1:c.3734C>T NP_001394775.1:p.Ala1245Val missense NM_001407847.1:c.3734C>T NP_001394776.1:p.Ala1245Val missense NM_001407848.1:c.3734C>T NP_001394777.1:p.Ala1245Val missense NM_001407849.1:c.3734C>T NP_001394778.1:p.Ala1245Val missense NM_001407850.1:c.3737C>T NP_001394779.1:p.Ala1246Val missense NM_001407851.1:c.3737C>T NP_001394780.1:p.Ala1246Val missense NM_001407852.1:c.3737C>T NP_001394781.1:p.Ala1246Val missense NM_001407853.1:c.3665C>T NP_001394782.1:p.Ala1222Val missense NM_001407854.1:c.3878C>T NP_001394783.1:p.Ala1293Val missense NM_001407858.1:c.3878C>T NP_001394787.1:p.Ala1293Val missense NM_001407859.1:c.3878C>T NP_001394788.1:p.Ala1293Val missense NM_001407860.1:c.3875C>T NP_001394789.1:p.Ala1292Val missense NM_001407861.1:c.3875C>T NP_001394790.1:p.Ala1292Val missense NM_001407862.1:c.3677C>T NP_001394791.1:p.Ala1226Val missense NM_001407863.1:c.3755C>T NP_001394792.1:p.Ala1252Val missense NM_001407874.1:c.3674C>T NP_001394803.1:p.Ala1225Val missense NM_001407875.1:c.3674C>T NP_001394804.1:p.Ala1225Val missense NM_001407879.1:c.3668C>T NP_001394808.1:p.Ala1223Val missense NM_001407881.1:c.3668C>T NP_001394810.1:p.Ala1223Val missense NM_001407882.1:c.3668C>T NP_001394811.1:p.Ala1223Val missense NM_001407884.1:c.3668C>T NP_001394813.1:p.Ala1223Val missense NM_001407885.1:c.3668C>T NP_001394814.1:p.Ala1223Val missense NM_001407886.1:c.3668C>T NP_001394815.1:p.Ala1223Val missense NM_001407887.1:c.3668C>T NP_001394816.1:p.Ala1223Val missense NM_001407889.1:c.3668C>T NP_001394818.1:p.Ala1223Val missense NM_001407894.1:c.3665C>T NP_001394823.1:p.Ala1222Val missense NM_001407895.1:c.3665C>T NP_001394824.1:p.Ala1222Val missense NM_001407896.1:c.3665C>T NP_001394825.1:p.Ala1222Val missense NM_001407897.1:c.3665C>T NP_001394826.1:p.Ala1222Val missense NM_001407898.1:c.3665C>T NP_001394827.1:p.Ala1222Val missense NM_001407899.1:c.3665C>T NP_001394828.1:p.Ala1222Val missense NM_001407900.1:c.3668C>T NP_001394829.1:p.Ala1223Val missense NM_001407902.1:c.3668C>T NP_001394831.1:p.Ala1223Val missense NM_001407904.1:c.3668C>T NP_001394833.1:p.Ala1223Val missense NM_001407906.1:c.3668C>T NP_001394835.1:p.Ala1223Val missense NM_001407907.1:c.3668C>T NP_001394836.1:p.Ala1223Val missense NM_001407908.1:c.3668C>T NP_001394837.1:p.Ala1223Val missense NM_001407909.1:c.3668C>T NP_001394838.1:p.Ala1223Val missense NM_001407910.1:c.3668C>T NP_001394839.1:p.Ala1223Val missense NM_001407915.1:c.3665C>T NP_001394844.1:p.Ala1222Val missense NM_001407916.1:c.3665C>T NP_001394845.1:p.Ala1222Val missense NM_001407917.1:c.3665C>T NP_001394846.1:p.Ala1222Val missense NM_001407918.1:c.3665C>T NP_001394847.1:p.Ala1222Val missense NM_001407919.1:c.3755C>T NP_001394848.1:p.Ala1252Val missense NM_001407920.1:c.3614C>T NP_001394849.1:p.Ala1205Val missense NM_001407921.1:c.3614C>T NP_001394850.1:p.Ala1205Val missense NM_001407922.1:c.3614C>T NP_001394851.1:p.Ala1205Val missense NM_001407923.1:c.3614C>T NP_001394852.1:p.Ala1205Val missense NM_001407924.1:c.3614C>T NP_001394853.1:p.Ala1205Val missense NM_001407925.1:c.3614C>T NP_001394854.1:p.Ala1205Val missense NM_001407926.1:c.3614C>T NP_001394855.1:p.Ala1205Val missense NM_001407927.1:c.3614C>T NP_001394856.1:p.Ala1205Val missense NM_001407928.1:c.3614C>T NP_001394857.1:p.Ala1205Val missense NM_001407929.1:c.3614C>T NP_001394858.1:p.Ala1205Val missense NM_001407930.1:c.3611C>T NP_001394859.1:p.Ala1204Val missense NM_001407931.1:c.3611C>T NP_001394860.1:p.Ala1204Val missense NM_001407932.1:c.3611C>T NP_001394861.1:p.Ala1204Val missense NM_001407933.1:c.3614C>T NP_001394862.1:p.Ala1205Val missense NM_001407934.1:c.3611C>T NP_001394863.1:p.Ala1204Val missense NM_001407935.1:c.3614C>T NP_001394864.1:p.Ala1205Val missense NM_001407936.1:c.3611C>T NP_001394865.1:p.Ala1204Val missense NM_001407937.1:c.3755C>T NP_001394866.1:p.Ala1252Val missense NM_001407938.1:c.3755C>T NP_001394867.1:p.Ala1252Val missense NM_001407939.1:c.3755C>T NP_001394868.1:p.Ala1252Val missense NM_001407940.1:c.3752C>T NP_001394869.1:p.Ala1251Val missense NM_001407941.1:c.3752C>T NP_001394870.1:p.Ala1251Val missense NM_001407942.1:c.3737C>T NP_001394871.1:p.Ala1246Val missense NM_001407943.1:c.3734C>T NP_001394872.1:p.Ala1245Val missense NM_001407944.1:c.3737C>T NP_001394873.1:p.Ala1246Val missense NM_001407945.1:c.3737C>T NP_001394874.1:p.Ala1246Val missense NM_001407946.1:c.3545C>T NP_001394875.1:p.Ala1182Val missense NM_001407947.1:c.3545C>T NP_001394876.1:p.Ala1182Val missense NM_001407948.1:c.3545C>T NP_001394877.1:p.Ala1182Val missense NM_001407949.1:c.3545C>T NP_001394878.1:p.Ala1182Val missense NM_001407950.1:c.3545C>T NP_001394879.1:p.Ala1182Val missense NM_001407951.1:c.3545C>T NP_001394880.1:p.Ala1182Val missense NM_001407952.1:c.3545C>T NP_001394881.1:p.Ala1182Val missense NM_001407953.1:c.3545C>T NP_001394882.1:p.Ala1182Val missense NM_001407954.1:c.3542C>T NP_001394883.1:p.Ala1181Val missense NM_001407955.1:c.3542C>T NP_001394884.1:p.Ala1181Val missense NM_001407956.1:c.3542C>T NP_001394885.1:p.Ala1181Val missense NM_001407957.1:c.3545C>T NP_001394886.1:p.Ala1182Val missense NM_001407958.1:c.3542C>T NP_001394887.1:p.Ala1181Val missense NM_001407959.1:c.3497C>T NP_001394888.1:p.Ala1166Val missense NM_001407960.1:c.3497C>T NP_001394889.1:p.Ala1166Val missense NM_001407962.1:c.3494C>T NP_001394891.1:p.Ala1165Val missense NM_001407963.1:c.3497C>T NP_001394892.1:p.Ala1166Val missense NM_001407964.1:c.3734C>T NP_001394893.1:p.Ala1245Val missense NM_001407965.1:c.3374C>T NP_001394894.1:p.Ala1125Val missense NM_001407966.1:c.2990C>T NP_001394895.1:p.Ala997Val missense NM_001407967.1:c.2990C>T NP_001394896.1:p.Ala997Val missense NM_001407968.1:c.1274C>T NP_001394897.1:p.Ala425Val missense NM_001407969.1:c.1274C>T NP_001394898.1:p.Ala425Val missense NM_001407970.1:c.788-621C>T intron variant NM_001407971.1:c.788-621C>T intron variant NM_001407972.1:c.785-621C>T intron variant NM_001407973.1:c.788-621C>T intron variant NM_001407974.1:c.788-621C>T intron variant NM_001407975.1:c.788-621C>T intron variant NM_001407976.1:c.788-621C>T intron variant NM_001407977.1:c.788-621C>T intron variant NM_001407978.1:c.788-621C>T intron variant NM_001407979.1:c.788-621C>T intron variant NM_001407980.1:c.788-621C>T intron variant NM_001407981.1:c.788-621C>T intron variant NM_001407982.1:c.788-621C>T intron variant NM_001407983.1:c.788-621C>T intron variant NM_001407984.1:c.785-621C>T intron variant NM_001407985.1:c.785-621C>T intron variant NM_001407986.1:c.785-621C>T intron variant NM_001407990.1:c.788-621C>T intron variant NM_001407991.1:c.785-621C>T intron variant NM_001407992.1:c.785-621C>T intron variant NM_001407993.1:c.788-621C>T intron variant NM_001408392.1:c.785-621C>T intron variant NM_001408396.1:c.785-621C>T intron variant NM_001408397.1:c.785-621C>T intron variant NM_001408398.1:c.785-621C>T intron variant NM_001408399.1:c.785-621C>T intron variant NM_001408400.1:c.785-621C>T intron variant NM_001408401.1:c.785-621C>T intron variant NM_001408402.1:c.785-621C>T intron variant NM_001408403.1:c.788-621C>T intron variant NM_001408404.1:c.788-621C>T intron variant NM_001408406.1:c.791-630C>T intron variant NM_001408407.1:c.785-621C>T intron variant NM_001408408.1:c.779-621C>T intron variant NM_001408409.1:c.710-621C>T intron variant NM_001408410.1:c.647-621C>T intron variant NM_001408411.1:c.710-621C>T intron variant NM_001408412.1:c.710-621C>T intron variant NM_001408413.1:c.707-621C>T intron variant NM_001408414.1:c.710-621C>T intron variant NM_001408415.1:c.710-621C>T intron variant NM_001408416.1:c.707-621C>T intron variant NM_001408418.1:c.671-621C>T intron variant NM_001408419.1:c.671-621C>T intron variant NM_001408420.1:c.671-621C>T intron variant NM_001408421.1:c.668-621C>T intron variant NM_001408422.1:c.671-621C>T intron variant NM_001408423.1:c.671-621C>T intron variant NM_001408424.1:c.668-621C>T intron variant NM_001408425.1:c.665-621C>T intron variant NM_001408426.1:c.665-621C>T intron variant NM_001408427.1:c.665-621C>T intron variant NM_001408428.1:c.665-621C>T intron variant NM_001408429.1:c.665-621C>T intron variant NM_001408430.1:c.665-621C>T intron variant NM_001408431.1:c.668-621C>T intron variant NM_001408432.1:c.662-621C>T intron variant NM_001408433.1:c.662-621C>T intron variant NM_001408434.1:c.662-621C>T intron variant NM_001408435.1:c.662-621C>T intron variant NM_001408436.1:c.665-621C>T intron variant NM_001408437.1:c.665-621C>T intron variant NM_001408438.1:c.665-621C>T intron variant NM_001408439.1:c.665-621C>T intron variant NM_001408440.1:c.665-621C>T intron variant NM_001408441.1:c.665-621C>T intron variant NM_001408442.1:c.665-621C>T intron variant NM_001408443.1:c.665-621C>T intron variant NM_001408444.1:c.665-621C>T intron variant NM_001408445.1:c.662-621C>T intron variant NM_001408446.1:c.662-621C>T intron variant NM_001408447.1:c.662-621C>T intron variant NM_001408448.1:c.662-621C>T intron variant NM_001408450.1:c.662-621C>T intron variant NM_001408451.1:c.653-621C>T intron variant NM_001408452.1:c.647-621C>T intron variant NM_001408453.1:c.647-621C>T intron variant NM_001408454.1:c.647-621C>T intron variant NM_001408455.1:c.647-621C>T intron variant NM_001408456.1:c.647-621C>T intron variant NM_001408457.1:c.647-621C>T intron variant NM_001408458.1:c.647-621C>T intron variant NM_001408459.1:c.647-621C>T intron variant NM_001408460.1:c.647-621C>T intron variant NM_001408461.1:c.647-621C>T intron variant NM_001408462.1:c.644-621C>T intron variant NM_001408463.1:c.644-621C>T intron variant NM_001408464.1:c.644-621C>T intron variant NM_001408465.1:c.644-621C>T intron variant NM_001408466.1:c.647-621C>T intron variant NM_001408467.1:c.647-621C>T intron variant NM_001408468.1:c.644-621C>T intron variant NM_001408469.1:c.647-621C>T intron variant NM_001408470.1:c.644-621C>T intron variant NM_001408472.1:c.788-621C>T intron variant NM_001408473.1:c.785-621C>T intron variant NM_001408474.1:c.587-621C>T intron variant NM_001408475.1:c.584-621C>T intron variant NM_001408476.1:c.587-621C>T intron variant NM_001408478.1:c.578-621C>T intron variant NM_001408479.1:c.578-621C>T intron variant NM_001408480.1:c.578-621C>T intron variant NM_001408481.1:c.578-621C>T intron variant NM_001408482.1:c.578-621C>T intron variant NM_001408483.1:c.578-621C>T intron variant NM_001408484.1:c.578-621C>T intron variant NM_001408485.1:c.578-621C>T intron variant NM_001408489.1:c.578-621C>T intron variant NM_001408490.1:c.575-621C>T intron variant NM_001408491.1:c.575-621C>T intron variant NM_001408492.1:c.578-621C>T intron variant NM_001408493.1:c.575-621C>T intron variant NM_001408494.1:c.548-621C>T intron variant NM_001408495.1:c.545-621C>T intron variant NM_001408496.1:c.524-621C>T intron variant NM_001408497.1:c.524-621C>T intron variant NM_001408498.1:c.524-621C>T intron variant NM_001408499.1:c.524-621C>T intron variant NM_001408500.1:c.524-621C>T intron variant NM_001408501.1:c.524-621C>T intron variant NM_001408502.1:c.455-621C>T intron variant NM_001408503.1:c.521-621C>T intron variant NM_001408504.1:c.521-621C>T intron variant NM_001408505.1:c.521-621C>T intron variant NM_001408506.1:c.461-621C>T intron variant NM_001408507.1:c.461-621C>T intron variant NM_001408508.1:c.452-621C>T intron variant NM_001408509.1:c.452-621C>T intron variant NM_001408510.1:c.407-621C>T intron variant NM_001408511.1:c.404-621C>T intron variant NM_001408512.1:c.284-621C>T intron variant NM_001408513.1:c.578-621C>T intron variant NM_001408514.1:c.578-621C>T intron variant NM_007297.4:c.3737C>T NP_009228.2:p.Ala1246Val missense NM_007298.4:c.788-621C>T intron variant NM_007299.4:c.788-621C>T intron variant NM_007300.4:c.3878C>T NP_009231.2:p.Ala1293Val missense NR_027676.1:n.4014C>T NC_000017.11:g.43091653G>A NC_000017.10:g.41243670G>A NG_005905.2:g.126331C>T NG_087068.1:g.635G>A LRG_292:g.126331C>T LRG_292t1:c.3878C>T LRG_292p1:p.Ala1293Val U14680.1:n.3997C>T - Protein change
- A1293V, A1246V, A1165V, A1222V, A1223V, A1226V, A1290V, A997V, A1181V, A1182V, A1204V, A1252V, A1266V, A1125V, A1205V, A1245V, A1251V, A1292V, A425V, A1166V, A1225V, A1267V
- Other names
-
3997C>T
- Canonical SPDI
- NC_000017.11:43091652:G: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.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- 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. |
|---|---|---|---|---|
| Uncertain significance (3) |
no assertion criteria provided
|
Sep 1, 2023 | RCV000077556.13 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Jun 7, 2023 | RCV000164922.15 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 23, 2023 | RCV001339366.13 | |
| Uncertain significance (1) |
no assertion criteria provided
|
- | RCV001355516.9 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Aug 23, 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: SCV001533106.4
First in ClinVar: Mar 22, 2021 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55036). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 30254663). This variant is present in population databases (rs80357213, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1293 of the BRCA1 protein (p.Ala1293Val). (less)
|
|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003849660.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
|
Uncertain significance
(Jun 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000215610.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.A1293V variant (also known as c.3878C>T and 3997C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution … (more)
The p.A1293V variant (also known as c.3878C>T and 3997C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3878. The alanine at codon 1293 is replaced by valine, an amino acid with similar properties. This alteration was identified in an individual from a hereditary breast and/or ovarian cancer cohort (Zuntini R et al. Front Genet 2018 Sep;9:378). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(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: SCV000144908.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550428.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
|
|
|
Uncertain significance
(Sep 01, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical and Surgical Sciences, University of Bologna
Accession: SCV004228354.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
PM2(Supporting)+PP4(Moderate)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
|
|
|
Uncertain significance
(Aug 19, 2009)
|
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: SCV000109358.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
|
Comment:
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
The p.A1293V variant (also known as c.3878C>T and 3997C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3878. The alanine at codon 1293 is replaced by valine, an amino acid with similar properties. This alteration was identified in an individual from a hereditary breast and/or ovarian cancer cohort (Zuntini R et al. Front Genet 2018 Sep;9:378). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
PM2(Supporting)+PP4(Moderate)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
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:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55036). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 30254663). This variant is present in population databases (rs80357213, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1293 of the BRCA1 protein (p.Ala1293Val).
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
The p.A1293V variant (also known as c.3878C>T and 3997C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3878. The alanine at codon 1293 is replaced by valine, an amino acid with similar properties. This alteration was identified in an individual from a hereditary breast and/or ovarian cancer cohort (Zuntini R et al. Front Genet 2018 Sep;9:378). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
PM2(Supporting)+PP4(Moderate)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
| Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help? | Zuntini R | Frontiers in genetics | 2018 | PMID: 30254663 |
Text-mined citations for rs80357213 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
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.