ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4654T>C (p.Tyr1552His)
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.
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.
Uncertain significance(6); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4654T>C (p.Tyr1552His)
Variation ID: 433716 Accession: VCV000433716.24
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074352 (GRCh38) [ NCBI UCSC ] 17: 41226369 (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 Aug 28, 2017 Apr 20, 2024 Oct 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.4654T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Tyr1552His missense NM_001407571.1:c.4441T>C NP_001394500.1:p.Tyr1481His missense NM_001407581.1:c.4720T>C NP_001394510.1:p.Tyr1574His missense NM_001407582.1:c.4720T>C NP_001394511.1:p.Tyr1574His missense NM_001407583.1:c.4717T>C NP_001394512.1:p.Tyr1573His missense NM_001407585.1:c.4717T>C NP_001394514.1:p.Tyr1573His missense NM_001407587.1:c.4717T>C NP_001394516.1:p.Tyr1573His missense NM_001407590.1:c.4714T>C NP_001394519.1:p.Tyr1572His missense NM_001407591.1:c.4714T>C NP_001394520.1:p.Tyr1572His missense NM_001407593.1:c.4654T>C NP_001394522.1:p.Tyr1552His missense NM_001407594.1:c.4654T>C NP_001394523.1:p.Tyr1552His missense NM_001407596.1:c.4654T>C NP_001394525.1:p.Tyr1552His missense NM_001407597.1:c.4654T>C NP_001394526.1:p.Tyr1552His missense NM_001407598.1:c.4654T>C NP_001394527.1:p.Tyr1552His missense NM_001407602.1:c.4654T>C NP_001394531.1:p.Tyr1552His missense NM_001407603.1:c.4654T>C NP_001394532.1:p.Tyr1552His missense NM_001407605.1:c.4654T>C NP_001394534.1:p.Tyr1552His missense NM_001407610.1:c.4651T>C NP_001394539.1:p.Tyr1551His missense NM_001407611.1:c.4651T>C NP_001394540.1:p.Tyr1551His missense NM_001407612.1:c.4651T>C NP_001394541.1:p.Tyr1551His missense NM_001407613.1:c.4651T>C NP_001394542.1:p.Tyr1551His missense NM_001407614.1:c.4651T>C NP_001394543.1:p.Tyr1551His missense NM_001407615.1:c.4651T>C NP_001394544.1:p.Tyr1551His missense NM_001407616.1:c.4651T>C NP_001394545.1:p.Tyr1551His missense NM_001407617.1:c.4651T>C NP_001394546.1:p.Tyr1551His missense NM_001407618.1:c.4651T>C NP_001394547.1:p.Tyr1551His missense NM_001407619.1:c.4651T>C NP_001394548.1:p.Tyr1551His missense NM_001407620.1:c.4651T>C NP_001394549.1:p.Tyr1551His missense NM_001407621.1:c.4651T>C NP_001394550.1:p.Tyr1551His missense NM_001407622.1:c.4651T>C NP_001394551.1:p.Tyr1551His missense NM_001407623.1:c.4651T>C NP_001394552.1:p.Tyr1551His missense NM_001407624.1:c.4651T>C NP_001394553.1:p.Tyr1551His missense NM_001407625.1:c.4651T>C NP_001394554.1:p.Tyr1551His missense NM_001407626.1:c.4651T>C NP_001394555.1:p.Tyr1551His missense NM_001407627.1:c.4648T>C NP_001394556.1:p.Tyr1550His missense NM_001407628.1:c.4648T>C NP_001394557.1:p.Tyr1550His missense NM_001407629.1:c.4648T>C NP_001394558.1:p.Tyr1550His missense NM_001407630.1:c.4648T>C NP_001394559.1:p.Tyr1550His missense NM_001407631.1:c.4648T>C NP_001394560.1:p.Tyr1550His missense NM_001407632.1:c.4648T>C NP_001394561.1:p.Tyr1550His missense NM_001407633.1:c.4648T>C NP_001394562.1:p.Tyr1550His missense NM_001407634.1:c.4648T>C NP_001394563.1:p.Tyr1550His missense NM_001407635.1:c.4648T>C NP_001394564.1:p.Tyr1550His missense NM_001407636.1:c.4648T>C NP_001394565.1:p.Tyr1550His missense NM_001407637.1:c.4648T>C NP_001394566.1:p.Tyr1550His missense NM_001407638.1:c.4648T>C NP_001394567.1:p.Tyr1550His missense NM_001407639.1:c.4648T>C NP_001394568.1:p.Tyr1550His missense NM_001407640.1:c.4648T>C NP_001394569.1:p.Tyr1550His missense NM_001407641.1:c.4648T>C NP_001394570.1:p.Tyr1550His missense NM_001407642.1:c.4648T>C NP_001394571.1:p.Tyr1550His missense NM_001407644.1:c.4645T>C NP_001394573.1:p.Tyr1549His missense NM_001407645.1:c.4645T>C NP_001394574.1:p.Tyr1549His missense NM_001407646.1:c.4642T>C NP_001394575.1:p.Tyr1548His missense NM_001407647.1:c.4639T>C NP_001394576.1:p.Tyr1547His missense NM_001407648.1:c.4597T>C NP_001394577.1:p.Tyr1533His missense NM_001407649.1:c.4594T>C NP_001394578.1:p.Tyr1532His missense NM_001407652.1:c.4654T>C NP_001394581.1:p.Tyr1552His missense NM_001407653.1:c.4576T>C NP_001394582.1:p.Tyr1526His missense NM_001407654.1:c.4576T>C NP_001394583.1:p.Tyr1526His missense NM_001407655.1:c.4576T>C NP_001394584.1:p.Tyr1526His missense NM_001407656.1:c.4573T>C NP_001394585.1:p.Tyr1525His missense NM_001407657.1:c.4573T>C NP_001394586.1:p.Tyr1525His missense NM_001407658.1:c.4573T>C NP_001394587.1:p.Tyr1525His missense NM_001407659.1:c.4570T>C NP_001394588.1:p.Tyr1524His missense NM_001407660.1:c.4570T>C NP_001394589.1:p.Tyr1524His missense NM_001407661.1:c.4570T>C NP_001394590.1:p.Tyr1524His missense NM_001407662.1:c.4570T>C NP_001394591.1:p.Tyr1524His missense NM_001407663.1:c.4570T>C NP_001394592.1:p.Tyr1524His missense NM_001407664.1:c.4531T>C NP_001394593.1:p.Tyr1511His missense NM_001407665.1:c.4531T>C NP_001394594.1:p.Tyr1511His missense NM_001407666.1:c.4531T>C NP_001394595.1:p.Tyr1511His missense NM_001407667.1:c.4531T>C NP_001394596.1:p.Tyr1511His missense NM_001407668.1:c.4531T>C NP_001394597.1:p.Tyr1511His missense NM_001407669.1:c.4531T>C NP_001394598.1:p.Tyr1511His missense NM_001407670.1:c.4528T>C NP_001394599.1:p.Tyr1510His missense NM_001407671.1:c.4528T>C NP_001394600.1:p.Tyr1510His missense NM_001407672.1:c.4528T>C NP_001394601.1:p.Tyr1510His missense NM_001407673.1:c.4528T>C NP_001394602.1:p.Tyr1510His missense NM_001407674.1:c.4528T>C NP_001394603.1:p.Tyr1510His missense NM_001407675.1:c.4528T>C NP_001394604.1:p.Tyr1510His missense NM_001407676.1:c.4528T>C NP_001394605.1:p.Tyr1510His missense NM_001407677.1:c.4528T>C NP_001394606.1:p.Tyr1510His missense NM_001407678.1:c.4528T>C NP_001394607.1:p.Tyr1510His missense NM_001407679.1:c.4528T>C NP_001394608.1:p.Tyr1510His missense NM_001407680.1:c.4528T>C NP_001394609.1:p.Tyr1510His missense NM_001407681.1:c.4525T>C NP_001394610.1:p.Tyr1509His missense NM_001407682.1:c.4525T>C NP_001394611.1:p.Tyr1509His missense NM_001407683.1:c.4525T>C NP_001394612.1:p.Tyr1509His missense NM_001407684.1:c.4654T>C NP_001394613.1:p.Tyr1552His missense NM_001407685.1:c.4525T>C NP_001394614.1:p.Tyr1509His missense NM_001407686.1:c.4525T>C NP_001394615.1:p.Tyr1509His missense NM_001407687.1:c.4525T>C NP_001394616.1:p.Tyr1509His missense NM_001407688.1:c.4525T>C NP_001394617.1:p.Tyr1509His missense NM_001407689.1:c.4525T>C NP_001394618.1:p.Tyr1509His missense NM_001407690.1:c.4522T>C NP_001394619.1:p.Tyr1508His missense NM_001407691.1:c.4522T>C NP_001394620.1:p.Tyr1508His missense NM_001407692.1:c.4513T>C NP_001394621.1:p.Tyr1505His missense NM_001407694.1:c.4513T>C NP_001394623.1:p.Tyr1505His missense NM_001407695.1:c.4513T>C NP_001394624.1:p.Tyr1505His missense NM_001407696.1:c.4513T>C NP_001394625.1:p.Tyr1505His missense NM_001407697.1:c.4513T>C NP_001394626.1:p.Tyr1505His missense NM_001407698.1:c.4513T>C NP_001394627.1:p.Tyr1505His missense NM_001407724.1:c.4513T>C NP_001394653.1:p.Tyr1505His missense NM_001407725.1:c.4513T>C NP_001394654.1:p.Tyr1505His missense NM_001407726.1:c.4513T>C NP_001394655.1:p.Tyr1505His missense NM_001407727.1:c.4513T>C NP_001394656.1:p.Tyr1505His missense NM_001407728.1:c.4513T>C NP_001394657.1:p.Tyr1505His missense NM_001407729.1:c.4513T>C NP_001394658.1:p.Tyr1505His missense NM_001407730.1:c.4513T>C NP_001394659.1:p.Tyr1505His missense NM_001407731.1:c.4513T>C NP_001394660.1:p.Tyr1505His missense NM_001407732.1:c.4510T>C NP_001394661.1:p.Tyr1504His missense NM_001407733.1:c.4510T>C NP_001394662.1:p.Tyr1504His missense NM_001407734.1:c.4510T>C NP_001394663.1:p.Tyr1504His missense NM_001407735.1:c.4510T>C NP_001394664.1:p.Tyr1504His missense NM_001407736.1:c.4510T>C NP_001394665.1:p.Tyr1504His missense NM_001407737.1:c.4510T>C NP_001394666.1:p.Tyr1504His missense NM_001407738.1:c.4510T>C NP_001394667.1:p.Tyr1504His missense NM_001407739.1:c.4510T>C NP_001394668.1:p.Tyr1504His missense NM_001407740.1:c.4510T>C NP_001394669.1:p.Tyr1504His missense NM_001407741.1:c.4510T>C NP_001394670.1:p.Tyr1504His missense NM_001407742.1:c.4510T>C NP_001394671.1:p.Tyr1504His missense NM_001407743.1:c.4510T>C NP_001394672.1:p.Tyr1504His missense NM_001407744.1:c.4510T>C NP_001394673.1:p.Tyr1504His missense NM_001407745.1:c.4510T>C NP_001394674.1:p.Tyr1504His missense NM_001407746.1:c.4510T>C NP_001394675.1:p.Tyr1504His missense NM_001407747.1:c.4510T>C NP_001394676.1:p.Tyr1504His missense NM_001407748.1:c.4510T>C NP_001394677.1:p.Tyr1504His missense NM_001407749.1:c.4510T>C NP_001394678.1:p.Tyr1504His missense NM_001407750.1:c.4510T>C NP_001394679.1:p.Tyr1504His missense NM_001407751.1:c.4510T>C NP_001394680.1:p.Tyr1504His missense NM_001407752.1:c.4510T>C NP_001394681.1:p.Tyr1504His missense NM_001407838.1:c.4507T>C NP_001394767.1:p.Tyr1503His missense NM_001407839.1:c.4507T>C NP_001394768.1:p.Tyr1503His missense NM_001407841.1:c.4507T>C NP_001394770.1:p.Tyr1503His missense NM_001407842.1:c.4507T>C NP_001394771.1:p.Tyr1503His missense NM_001407843.1:c.4507T>C NP_001394772.1:p.Tyr1503His missense NM_001407844.1:c.4507T>C NP_001394773.1:p.Tyr1503His missense NM_001407845.1:c.4507T>C NP_001394774.1:p.Tyr1503His missense NM_001407846.1:c.4507T>C NP_001394775.1:p.Tyr1503His missense NM_001407847.1:c.4507T>C NP_001394776.1:p.Tyr1503His missense NM_001407848.1:c.4507T>C NP_001394777.1:p.Tyr1503His missense NM_001407849.1:c.4507T>C NP_001394778.1:p.Tyr1503His missense NM_001407850.1:c.4507T>C NP_001394779.1:p.Tyr1503His missense NM_001407851.1:c.4507T>C NP_001394780.1:p.Tyr1503His missense NM_001407852.1:c.4507T>C NP_001394781.1:p.Tyr1503His missense NM_001407853.1:c.4507T>C NP_001394782.1:p.Tyr1503His missense NM_001407854.1:c.4654T>C NP_001394783.1:p.Tyr1552His missense NM_001407858.1:c.4651T>C NP_001394787.1:p.Tyr1551His missense NM_001407859.1:c.4651T>C NP_001394788.1:p.Tyr1551His missense NM_001407860.1:c.4651T>C NP_001394789.1:p.Tyr1551His missense NM_001407861.1:c.4648T>C NP_001394790.1:p.Tyr1550His missense NM_001407862.1:c.4453T>C NP_001394791.1:p.Tyr1485His missense NM_001407863.1:c.4528T>C NP_001394792.1:p.Tyr1510His missense NM_001407874.1:c.4447T>C NP_001394803.1:p.Tyr1483His missense NM_001407875.1:c.4447T>C NP_001394804.1:p.Tyr1483His missense NM_001407879.1:c.4444T>C NP_001394808.1:p.Tyr1482His missense NM_001407881.1:c.4444T>C NP_001394810.1:p.Tyr1482His missense NM_001407882.1:c.4444T>C NP_001394811.1:p.Tyr1482His missense NM_001407884.1:c.4444T>C NP_001394813.1:p.Tyr1482His missense NM_001407885.1:c.4444T>C NP_001394814.1:p.Tyr1482His missense NM_001407886.1:c.4444T>C NP_001394815.1:p.Tyr1482His missense NM_001407887.1:c.4444T>C NP_001394816.1:p.Tyr1482His missense NM_001407889.1:c.4444T>C NP_001394818.1:p.Tyr1482His missense NM_001407894.1:c.4441T>C NP_001394823.1:p.Tyr1481His missense NM_001407895.1:c.4441T>C NP_001394824.1:p.Tyr1481His missense NM_001407896.1:c.4441T>C NP_001394825.1:p.Tyr1481His missense NM_001407897.1:c.4441T>C NP_001394826.1:p.Tyr1481His missense NM_001407898.1:c.4441T>C NP_001394827.1:p.Tyr1481His missense NM_001407899.1:c.4441T>C NP_001394828.1:p.Tyr1481His missense NM_001407900.1:c.4441T>C NP_001394829.1:p.Tyr1481His missense NM_001407902.1:c.4441T>C NP_001394831.1:p.Tyr1481His missense NM_001407904.1:c.4441T>C NP_001394833.1:p.Tyr1481His missense NM_001407906.1:c.4441T>C NP_001394835.1:p.Tyr1481His missense NM_001407907.1:c.4441T>C NP_001394836.1:p.Tyr1481His missense NM_001407908.1:c.4441T>C NP_001394837.1:p.Tyr1481His missense NM_001407909.1:c.4441T>C NP_001394838.1:p.Tyr1481His missense NM_001407910.1:c.4441T>C NP_001394839.1:p.Tyr1481His missense NM_001407915.1:c.4438T>C NP_001394844.1:p.Tyr1480His missense NM_001407916.1:c.4438T>C NP_001394845.1:p.Tyr1480His missense NM_001407917.1:c.4438T>C NP_001394846.1:p.Tyr1480His missense NM_001407918.1:c.4438T>C NP_001394847.1:p.Tyr1480His missense NM_001407919.1:c.4531T>C NP_001394848.1:p.Tyr1511His missense NM_001407920.1:c.4390T>C NP_001394849.1:p.Tyr1464His missense NM_001407921.1:c.4390T>C NP_001394850.1:p.Tyr1464His missense NM_001407922.1:c.4390T>C NP_001394851.1:p.Tyr1464His missense NM_001407923.1:c.4390T>C NP_001394852.1:p.Tyr1464His missense NM_001407924.1:c.4390T>C NP_001394853.1:p.Tyr1464His missense NM_001407925.1:c.4390T>C NP_001394854.1:p.Tyr1464His missense NM_001407926.1:c.4390T>C NP_001394855.1:p.Tyr1464His missense NM_001407927.1:c.4387T>C NP_001394856.1:p.Tyr1463His missense NM_001407928.1:c.4387T>C NP_001394857.1:p.Tyr1463His missense NM_001407929.1:c.4387T>C NP_001394858.1:p.Tyr1463His missense NM_001407930.1:c.4387T>C NP_001394859.1:p.Tyr1463His missense NM_001407931.1:c.4387T>C NP_001394860.1:p.Tyr1463His missense NM_001407932.1:c.4387T>C NP_001394861.1:p.Tyr1463His missense NM_001407933.1:c.4387T>C NP_001394862.1:p.Tyr1463His missense NM_001407934.1:c.4384T>C NP_001394863.1:p.Tyr1462His missense NM_001407935.1:c.4384T>C NP_001394864.1:p.Tyr1462His missense NM_001407936.1:c.4384T>C NP_001394865.1:p.Tyr1462His missense NM_001407937.1:c.4531T>C NP_001394866.1:p.Tyr1511His missense NM_001407938.1:c.4531T>C NP_001394867.1:p.Tyr1511His missense NM_001407939.1:c.4528T>C NP_001394868.1:p.Tyr1510His missense NM_001407940.1:c.4528T>C NP_001394869.1:p.Tyr1510His missense NM_001407941.1:c.4525T>C NP_001394870.1:p.Tyr1509His missense NM_001407942.1:c.4513T>C NP_001394871.1:p.Tyr1505His missense NM_001407943.1:c.4510T>C NP_001394872.1:p.Tyr1504His missense NM_001407944.1:c.4510T>C NP_001394873.1:p.Tyr1504His missense NM_001407945.1:c.4510T>C NP_001394874.1:p.Tyr1504His missense NM_001407946.1:c.4321T>C NP_001394875.1:p.Tyr1441His missense NM_001407947.1:c.4321T>C NP_001394876.1:p.Tyr1441His missense NM_001407948.1:c.4321T>C NP_001394877.1:p.Tyr1441His missense NM_001407949.1:c.4321T>C NP_001394878.1:p.Tyr1441His missense NM_001407950.1:c.4318T>C NP_001394879.1:p.Tyr1440His missense NM_001407951.1:c.4318T>C NP_001394880.1:p.Tyr1440His missense NM_001407952.1:c.4318T>C NP_001394881.1:p.Tyr1440His missense NM_001407953.1:c.4318T>C NP_001394882.1:p.Tyr1440His missense NM_001407954.1:c.4318T>C NP_001394883.1:p.Tyr1440His missense NM_001407955.1:c.4318T>C NP_001394884.1:p.Tyr1440His missense NM_001407956.1:c.4315T>C NP_001394885.1:p.Tyr1439His missense NM_001407957.1:c.4315T>C NP_001394886.1:p.Tyr1439His missense NM_001407958.1:c.4315T>C NP_001394887.1:p.Tyr1439His missense NM_001407959.1:c.4273T>C NP_001394888.1:p.Tyr1425His missense NM_001407960.1:c.4270T>C NP_001394889.1:p.Tyr1424His missense NM_001407962.1:c.4270T>C NP_001394891.1:p.Tyr1424His missense NM_001407963.1:c.4267T>C NP_001394892.1:p.Tyr1423His missense NM_001407965.1:c.4147T>C NP_001394894.1:p.Tyr1383His missense NM_001407966.1:c.3766T>C NP_001394895.1:p.Tyr1256His missense NM_001407967.1:c.3763T>C NP_001394896.1:p.Tyr1255His missense NM_001407968.1:c.2050T>C NP_001394897.1:p.Tyr684His missense NM_001407969.1:c.2047T>C NP_001394898.1:p.Tyr683His missense NM_001407970.1:c.1411T>C NP_001394899.1:p.Tyr471His missense NM_001407971.1:c.1411T>C NP_001394900.1:p.Tyr471His missense NM_001407972.1:c.1408T>C NP_001394901.1:p.Tyr470His missense NM_001407973.1:c.1345T>C NP_001394902.1:p.Tyr449His missense NM_001407974.1:c.1345T>C NP_001394903.1:p.Tyr449His missense NM_001407975.1:c.1345T>C NP_001394904.1:p.Tyr449His missense NM_001407976.1:c.1345T>C NP_001394905.1:p.Tyr449His missense NM_001407977.1:c.1345T>C NP_001394906.1:p.Tyr449His missense NM_001407978.1:c.1345T>C NP_001394907.1:p.Tyr449His missense NM_001407979.1:c.1342T>C NP_001394908.1:p.Tyr448His missense NM_001407980.1:c.1342T>C NP_001394909.1:p.Tyr448His missense NM_001407981.1:c.1342T>C NP_001394910.1:p.Tyr448His missense NM_001407982.1:c.1342T>C NP_001394911.1:p.Tyr448His missense NM_001407983.1:c.1342T>C NP_001394912.1:p.Tyr448His missense NM_001407984.1:c.1342T>C NP_001394913.1:p.Tyr448His missense NM_001407985.1:c.1342T>C NP_001394914.1:p.Tyr448His missense NM_001407986.1:c.1342T>C NP_001394915.1:p.Tyr448His missense NM_001407990.1:c.1342T>C NP_001394919.1:p.Tyr448His missense NM_001407991.1:c.1342T>C NP_001394920.1:p.Tyr448His missense NM_001407992.1:c.1342T>C NP_001394921.1:p.Tyr448His missense NM_001407993.1:c.1342T>C NP_001394922.1:p.Tyr448His missense NM_001408392.1:c.1339T>C NP_001395321.1:p.Tyr447His missense NM_001408396.1:c.1339T>C NP_001395325.1:p.Tyr447His missense NM_001408397.1:c.1339T>C NP_001395326.1:p.Tyr447His missense NM_001408398.1:c.1339T>C NP_001395327.1:p.Tyr447His missense NM_001408399.1:c.1339T>C NP_001395328.1:p.Tyr447His missense NM_001408400.1:c.1339T>C NP_001395329.1:p.Tyr447His missense NM_001408401.1:c.1339T>C NP_001395330.1:p.Tyr447His missense NM_001408402.1:c.1339T>C NP_001395331.1:p.Tyr447His missense NM_001408403.1:c.1339T>C NP_001395332.1:p.Tyr447His missense NM_001408404.1:c.1339T>C NP_001395333.1:p.Tyr447His missense NM_001408406.1:c.1336T>C NP_001395335.1:p.Tyr446His missense NM_001408407.1:c.1336T>C NP_001395336.1:p.Tyr446His missense NM_001408408.1:c.1336T>C NP_001395337.1:p.Tyr446His missense NM_001408409.1:c.1333T>C NP_001395338.1:p.Tyr445His missense NM_001408410.1:c.1270T>C NP_001395339.1:p.Tyr424His missense NM_001408411.1:c.1267T>C NP_001395340.1:p.Tyr423His missense NM_001408412.1:c.1264T>C NP_001395341.1:p.Tyr422His missense NM_001408413.1:c.1264T>C NP_001395342.1:p.Tyr422His missense NM_001408414.1:c.1264T>C NP_001395343.1:p.Tyr422His missense NM_001408415.1:c.1264T>C NP_001395344.1:p.Tyr422His missense NM_001408416.1:c.1264T>C NP_001395345.1:p.Tyr422His missense NM_001408418.1:c.1228T>C NP_001395347.1:p.Tyr410His missense NM_001408419.1:c.1228T>C NP_001395348.1:p.Tyr410His missense NM_001408420.1:c.1228T>C NP_001395349.1:p.Tyr410His missense NM_001408421.1:c.1225T>C NP_001395350.1:p.Tyr409His missense NM_001408422.1:c.1225T>C NP_001395351.1:p.Tyr409His missense NM_001408423.1:c.1225T>C NP_001395352.1:p.Tyr409His missense NM_001408424.1:c.1225T>C NP_001395353.1:p.Tyr409His missense NM_001408425.1:c.1222T>C NP_001395354.1:p.Tyr408His missense NM_001408426.1:c.1222T>C NP_001395355.1:p.Tyr408His missense NM_001408427.1:c.1222T>C NP_001395356.1:p.Tyr408His missense NM_001408428.1:c.1222T>C NP_001395357.1:p.Tyr408His missense NM_001408429.1:c.1222T>C NP_001395358.1:p.Tyr408His missense NM_001408430.1:c.1222T>C NP_001395359.1:p.Tyr408His missense NM_001408431.1:c.1222T>C NP_001395360.1:p.Tyr408His missense NM_001408432.1:c.1219T>C NP_001395361.1:p.Tyr407His missense NM_001408433.1:c.1219T>C NP_001395362.1:p.Tyr407His missense NM_001408434.1:c.1219T>C NP_001395363.1:p.Tyr407His missense NM_001408435.1:c.1219T>C NP_001395364.1:p.Tyr407His missense NM_001408436.1:c.1219T>C NP_001395365.1:p.Tyr407His missense NM_001408437.1:c.1219T>C NP_001395366.1:p.Tyr407His missense NM_001408438.1:c.1219T>C NP_001395367.1:p.Tyr407His missense NM_001408439.1:c.1219T>C NP_001395368.1:p.Tyr407His missense NM_001408440.1:c.1219T>C NP_001395369.1:p.Tyr407His missense NM_001408441.1:c.1219T>C NP_001395370.1:p.Tyr407His missense NM_001408442.1:c.1219T>C NP_001395371.1:p.Tyr407His missense NM_001408443.1:c.1219T>C NP_001395372.1:p.Tyr407His missense NM_001408444.1:c.1219T>C NP_001395373.1:p.Tyr407His missense NM_001408445.1:c.1216T>C NP_001395374.1:p.Tyr406His missense NM_001408446.1:c.1216T>C NP_001395375.1:p.Tyr406His missense NM_001408447.1:c.1216T>C NP_001395376.1:p.Tyr406His missense NM_001408448.1:c.1216T>C NP_001395377.1:p.Tyr406His missense NM_001408450.1:c.1216T>C NP_001395379.1:p.Tyr406His missense NM_001408451.1:c.1210T>C NP_001395380.1:p.Tyr404His missense NM_001408452.1:c.1204T>C NP_001395381.1:p.Tyr402His missense NM_001408453.1:c.1204T>C NP_001395382.1:p.Tyr402His missense NM_001408454.1:c.1204T>C NP_001395383.1:p.Tyr402His missense NM_001408455.1:c.1204T>C NP_001395384.1:p.Tyr402His missense NM_001408456.1:c.1204T>C NP_001395385.1:p.Tyr402His missense NM_001408457.1:c.1204T>C NP_001395386.1:p.Tyr402His missense NM_001408458.1:c.1201T>C NP_001395387.1:p.Tyr401His missense NM_001408459.1:c.1201T>C NP_001395388.1:p.Tyr401His missense NM_001408460.1:c.1201T>C NP_001395389.1:p.Tyr401His missense NM_001408461.1:c.1201T>C NP_001395390.1:p.Tyr401His missense NM_001408462.1:c.1201T>C NP_001395391.1:p.Tyr401His missense NM_001408463.1:c.1201T>C NP_001395392.1:p.Tyr401His missense NM_001408464.1:c.1201T>C NP_001395393.1:p.Tyr401His missense NM_001408465.1:c.1201T>C NP_001395394.1:p.Tyr401His missense NM_001408466.1:c.1201T>C NP_001395395.1:p.Tyr401His missense NM_001408467.1:c.1201T>C NP_001395396.1:p.Tyr401His missense NM_001408468.1:c.1198T>C NP_001395397.1:p.Tyr400His missense NM_001408469.1:c.1198T>C NP_001395398.1:p.Tyr400His missense NM_001408470.1:c.1198T>C NP_001395399.1:p.Tyr400His missense NM_001408472.1:c.1342T>C NP_001395401.1:p.Tyr448His missense NM_001408473.1:c.1339T>C NP_001395402.1:p.Tyr447His missense NM_001408474.1:c.1144T>C NP_001395403.1:p.Tyr382His missense NM_001408475.1:c.1141T>C NP_001395404.1:p.Tyr381His missense NM_001408476.1:c.1141T>C NP_001395405.1:p.Tyr381His missense NM_001408478.1:c.1135T>C NP_001395407.1:p.Tyr379His missense NM_001408479.1:c.1135T>C NP_001395408.1:p.Tyr379His missense NM_001408480.1:c.1135T>C NP_001395409.1:p.Tyr379His missense NM_001408481.1:c.1132T>C NP_001395410.1:p.Tyr378His missense NM_001408482.1:c.1132T>C NP_001395411.1:p.Tyr378His missense NM_001408483.1:c.1132T>C NP_001395412.1:p.Tyr378His missense NM_001408484.1:c.1132T>C NP_001395413.1:p.Tyr378His missense NM_001408485.1:c.1132T>C NP_001395414.1:p.Tyr378His missense NM_001408489.1:c.1132T>C NP_001395418.1:p.Tyr378His missense NM_001408490.1:c.1132T>C NP_001395419.1:p.Tyr378His missense NM_001408491.1:c.1132T>C NP_001395420.1:p.Tyr378His missense NM_001408492.1:c.1129T>C NP_001395421.1:p.Tyr377His missense NM_001408493.1:c.1129T>C NP_001395422.1:p.Tyr377His missense NM_001408494.1:c.1105T>C NP_001395423.1:p.Tyr369His missense NM_001408495.1:c.1099T>C NP_001395424.1:p.Tyr367His missense NM_001408496.1:c.1081T>C NP_001395425.1:p.Tyr361His missense NM_001408497.1:c.1081T>C NP_001395426.1:p.Tyr361His missense NM_001408498.1:c.1081T>C NP_001395427.1:p.Tyr361His missense NM_001408499.1:c.1081T>C NP_001395428.1:p.Tyr361His missense NM_001408500.1:c.1081T>C NP_001395429.1:p.Tyr361His missense NM_001408501.1:c.1081T>C NP_001395430.1:p.Tyr361His missense NM_001408502.1:c.1078T>C NP_001395431.1:p.Tyr360His missense NM_001408503.1:c.1078T>C NP_001395432.1:p.Tyr360His missense NM_001408504.1:c.1078T>C NP_001395433.1:p.Tyr360His missense NM_001408505.1:c.1075T>C NP_001395434.1:p.Tyr359His missense NM_001408506.1:c.1018T>C NP_001395435.1:p.Tyr340His missense NM_001408507.1:c.1015T>C NP_001395436.1:p.Tyr339His missense NM_001408508.1:c.1006T>C NP_001395437.1:p.Tyr336His missense NM_001408509.1:c.1003T>C NP_001395438.1:p.Tyr335His missense NM_001408510.1:c.964T>C NP_001395439.1:p.Tyr322His missense NM_001408511.1:c.961T>C NP_001395440.1:p.Tyr321His missense NM_001408512.1:c.841T>C NP_001395441.1:p.Tyr281His missense NM_007297.4:c.4513T>C NP_009228.2:p.Tyr1505His missense NM_007298.4:c.1342T>C NP_009229.2:p.Tyr448His missense NM_007299.4:c.1342T>C NP_009230.2:p.Tyr448His missense NM_007300.4:c.4717T>C NP_009231.2:p.Tyr1573His missense NM_007304.2:c.1342T>C NP_009235.2:p.Tyr448His missense NR_027676.2:n.4831T>C non-coding transcript variant NC_000017.11:g.43074352A>G NC_000017.10:g.41226369A>G NG_005905.2:g.143632T>C LRG_292:g.143632T>C LRG_292t1:c.4654T>C LRG_292p1:p.Tyr1552His - Protein change
- Y1552H, Y1505H, Y448H, Y1573H, Y1256H, Y1463H, Y1483H, Y1525H, Y1533H, Y1549H, Y1550H, Y1574H, Y336H, Y360H, Y379H, Y404H, Y406H, Y408H, Y422H, Y423H, Y447H, Y1424H, Y1439H, Y1440H, Y1482H, Y1548H, Y1551H, Y322H, Y340H, Y367H, Y369H, Y381H, Y402H, Y407H, Y471H, Y683H, Y1383H, Y1423H, Y1464H, Y1509H, Y1510H, Y1526H, Y339H, Y359H, Y378H, Y400H, Y401H, Y409H, Y424H, Y446H, Y684H, Y1255H, Y1425H, Y1441H, Y1462H, Y1480H, Y1481H, Y1485H, Y1503H, Y1504H, Y1508H, Y1511H, Y1524H, Y1532H, Y1547H, Y1572H, Y281H, Y321H, Y335H, Y361H, Y377H, Y382H, Y410H, Y445H, Y449H, Y470H
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074351:A:G
-
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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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 |
12795 | 14565 |
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 (1) |
no assertion criteria provided
|
- | RCV000504104.3 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 14, 2023 | RCV000532651.9 | |
Likely benign (1) |
no assertion criteria provided
|
Oct 3, 2013 | RCV000735520.2 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Sep 23, 2022 | RCV000758836.5 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000765359.3 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Jun 26, 2023 | RCV000776618.9 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Aug 23, 2023 | RCV003330731.1 | |
Likely benign (1) |
criteria provided, single submitter
|
May 4, 2023 | RCV004003514.1 |
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
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000896624.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
Likely benign
(Oct 07, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000912236.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
Uncertain significance
(Jan 02, 2022)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002537765.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
Uncertain significance
(Aug 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004039195.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Variant summary: BRCA1 c.4654T>C (p.Tyr1552His) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: BRCA1 c.4654T>C (p.Tyr1552His) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251256 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4654T>C has been reported in the literature in individuals affected with Melanoma or Breast and/or Ovarian Cancer without strong evidence for causality (examples, Goldstein_2017, Jalkh_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29036293, 22713736). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (VUS, n=5, Likely benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
|
Uncertain significance
(Jun 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001184632.4
First in ClinVar: Mar 16, 2020 Last updated: Oct 28, 2023 |
Comment:
The p.Y1552H variant (also known as c.4654T>C), located in coding exon 13 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.Y1552H variant (also known as c.4654T>C), located in coding exon 13 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4654. The tyrosine at codon 1552 is replaced by histidine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with melanoma (Goldstein AM et al. Hum Mol Genet, 2017 12;26:4886-4895) and in an individual with a family history of breast and/or ovarian cancer from Lebanon (Jalkh N et al. Hered Cancer Clin Pract, 2012 Jun;10:7). This amino acid position is not well 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)
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Uncertain significance
(Sep 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000887705.4
First in ClinVar: Mar 14, 2019 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.000004 (1/251256 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the … (more)
The frequency of this variant in the general population, 0.000004 (1/251256 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals affected with breast/ovarian cancer (PMID: 22713736 (2012)) and melanoma (PMID: 29036293 (2017)). One in vitro study showed that the wild- type tyrosine residue at this position is important for BRCA1 stability and function in DNA repair (PMID: 29156836 (2017)). However, additional functional studies are needed to assess the effect of this variant. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Uncertain significance
(Oct 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000635985.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1552 of the BRCA1 protein (p.Tyr1552His). … (more)
This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1552 of the BRCA1 protein (p.Tyr1552His). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast cancer and cutaneous malignant melanoma (PMID: 22713736, 29036293). This variant is also known as 4773T>C. ClinVar contains an entry for this variant (Variation ID: 433716). 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. 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. (less)
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Likely Benign
(May 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004817644.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Number of individuals with the variant: 1
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Likely benign
(Oct 03, 2013)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863658.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591531.2 First in ClinVar: Aug 28, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA1 p.Tyr1552His variant was identified by Jalkh (2012) in a Lebanese individual with breast cancer. The variant was also identified in UMD (2X as … (more)
The BRCA1 p.Tyr1552His variant was identified by Jalkh (2012) in a Lebanese individual with breast cancer. The variant was also identified in UMD (2X as an unclassified variant); in one of these samples it was found in co-occurrence with a pathogenic BRCA1 mutation (c.4358_4484del (p.Ala1453GlyfsX10)), increasing the likelihood that the p.Tyr1552His variant does not have clinical significance. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The p.Ala469Thr residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of unknown significance. (less)
Number of individuals with the variant: 1
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Rare germline variants in known melanoma susceptibility genes in familial melanoma. | Goldstein AM | Human molecular genetics | 2017 | PMID: 29036293 |
The role of Rak in the regulation of stability and function of BRCA1. | Kim JL | Oncotarget | 2015 | PMID: 29156836 |
Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon. | Jalkh N | Hereditary cancer in clinical practice | 2012 | PMID: 22713736 |
Text-mined citations for rs1265352633 ...
HelpRecord last updated Apr 20, 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.