This variant is denoted BRCA1 c.3752G>A at the cDNA level, p.Cys1251Tyr (C1251Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGT>TAT). Using alternate nomenclature, this variant would be defined as BRCA1 3871G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Cys1251Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Cysteine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Cys1251Tyr occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Cys1251Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3752G>A (p.Cys1251Tyr)
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.
(4)
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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(3); Likely benign(1)
Uncertain significance(3); Likely benign(1)
4
criteria provided, conflicting classifications
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.3752G>A (p.Cys1251Tyr)
Variation ID: 246072 Accession: VCV000246072.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091779 (GRCh38) [ NCBI UCSC ] 17: 41243796 (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 Jul 25, 2016 Feb 28, 2024 Mar 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3752G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Cys1251Tyr missense NM_001407571.1:c.3539G>A NP_001394500.1:p.Cys1180Tyr missense NM_001407581.1:c.3752G>A NP_001394510.1:p.Cys1251Tyr missense NM_001407582.1:c.3752G>A NP_001394511.1:p.Cys1251Tyr missense NM_001407583.1:c.3752G>A NP_001394512.1:p.Cys1251Tyr missense NM_001407585.1:c.3752G>A NP_001394514.1:p.Cys1251Tyr missense NM_001407587.1:c.3749G>A NP_001394516.1:p.Cys1250Tyr missense NM_001407590.1:c.3749G>A NP_001394519.1:p.Cys1250Tyr missense NM_001407591.1:c.3749G>A NP_001394520.1:p.Cys1250Tyr missense NM_001407593.1:c.3752G>A NP_001394522.1:p.Cys1251Tyr missense NM_001407594.1:c.3752G>A NP_001394523.1:p.Cys1251Tyr missense NM_001407596.1:c.3752G>A NP_001394525.1:p.Cys1251Tyr missense NM_001407597.1:c.3752G>A NP_001394526.1:p.Cys1251Tyr missense NM_001407598.1:c.3752G>A NP_001394527.1:p.Cys1251Tyr missense NM_001407602.1:c.3752G>A NP_001394531.1:p.Cys1251Tyr missense NM_001407603.1:c.3752G>A NP_001394532.1:p.Cys1251Tyr missense NM_001407605.1:c.3752G>A NP_001394534.1:p.Cys1251Tyr missense NM_001407610.1:c.3749G>A NP_001394539.1:p.Cys1250Tyr missense NM_001407611.1:c.3749G>A NP_001394540.1:p.Cys1250Tyr missense NM_001407612.1:c.3749G>A NP_001394541.1:p.Cys1250Tyr missense NM_001407613.1:c.3749G>A NP_001394542.1:p.Cys1250Tyr missense NM_001407614.1:c.3749G>A NP_001394543.1:p.Cys1250Tyr missense NM_001407615.1:c.3749G>A NP_001394544.1:p.Cys1250Tyr missense NM_001407616.1:c.3752G>A NP_001394545.1:p.Cys1251Tyr missense NM_001407617.1:c.3752G>A NP_001394546.1:p.Cys1251Tyr missense NM_001407618.1:c.3752G>A NP_001394547.1:p.Cys1251Tyr missense NM_001407619.1:c.3752G>A NP_001394548.1:p.Cys1251Tyr missense NM_001407620.1:c.3752G>A NP_001394549.1:p.Cys1251Tyr missense NM_001407621.1:c.3752G>A NP_001394550.1:p.Cys1251Tyr missense NM_001407622.1:c.3752G>A NP_001394551.1:p.Cys1251Tyr missense NM_001407623.1:c.3752G>A NP_001394552.1:p.Cys1251Tyr missense NM_001407624.1:c.3752G>A NP_001394553.1:p.Cys1251Tyr missense NM_001407625.1:c.3752G>A NP_001394554.1:p.Cys1251Tyr missense NM_001407626.1:c.3752G>A NP_001394555.1:p.Cys1251Tyr missense NM_001407627.1:c.3749G>A NP_001394556.1:p.Cys1250Tyr missense NM_001407628.1:c.3749G>A NP_001394557.1:p.Cys1250Tyr missense NM_001407629.1:c.3749G>A NP_001394558.1:p.Cys1250Tyr missense NM_001407630.1:c.3749G>A NP_001394559.1:p.Cys1250Tyr missense NM_001407631.1:c.3749G>A NP_001394560.1:p.Cys1250Tyr missense NM_001407632.1:c.3749G>A NP_001394561.1:p.Cys1250Tyr missense NM_001407633.1:c.3749G>A NP_001394562.1:p.Cys1250Tyr missense NM_001407634.1:c.3749G>A NP_001394563.1:p.Cys1250Tyr missense NM_001407635.1:c.3749G>A NP_001394564.1:p.Cys1250Tyr missense NM_001407636.1:c.3749G>A NP_001394565.1:p.Cys1250Tyr missense NM_001407637.1:c.3749G>A NP_001394566.1:p.Cys1250Tyr missense NM_001407638.1:c.3749G>A NP_001394567.1:p.Cys1250Tyr missense NM_001407639.1:c.3752G>A NP_001394568.1:p.Cys1251Tyr missense NM_001407640.1:c.3752G>A NP_001394569.1:p.Cys1251Tyr missense NM_001407641.1:c.3752G>A NP_001394570.1:p.Cys1251Tyr missense NM_001407642.1:c.3752G>A NP_001394571.1:p.Cys1251Tyr missense NM_001407644.1:c.3749G>A NP_001394573.1:p.Cys1250Tyr missense NM_001407645.1:c.3749G>A NP_001394574.1:p.Cys1250Tyr missense NM_001407646.1:c.3743G>A NP_001394575.1:p.Cys1248Tyr missense NM_001407647.1:c.3743G>A NP_001394576.1:p.Cys1248Tyr missense NM_001407648.1:c.3629G>A NP_001394577.1:p.Cys1210Tyr missense NM_001407649.1:c.3626G>A NP_001394578.1:p.Cys1209Tyr missense NM_001407652.1:c.3752G>A NP_001394581.1:p.Cys1251Tyr missense NM_001407653.1:c.3674G>A NP_001394582.1:p.Cys1225Tyr missense NM_001407654.1:c.3674G>A NP_001394583.1:p.Cys1225Tyr missense NM_001407655.1:c.3674G>A NP_001394584.1:p.Cys1225Tyr missense NM_001407656.1:c.3674G>A NP_001394585.1:p.Cys1225Tyr missense NM_001407657.1:c.3674G>A NP_001394586.1:p.Cys1225Tyr missense NM_001407658.1:c.3674G>A NP_001394587.1:p.Cys1225Tyr missense NM_001407659.1:c.3671G>A NP_001394588.1:p.Cys1224Tyr missense NM_001407660.1:c.3671G>A NP_001394589.1:p.Cys1224Tyr missense NM_001407661.1:c.3671G>A NP_001394590.1:p.Cys1224Tyr missense NM_001407662.1:c.3671G>A NP_001394591.1:p.Cys1224Tyr missense NM_001407663.1:c.3674G>A NP_001394592.1:p.Cys1225Tyr missense NM_001407664.1:c.3629G>A NP_001394593.1:p.Cys1210Tyr missense NM_001407665.1:c.3629G>A NP_001394594.1:p.Cys1210Tyr missense NM_001407666.1:c.3629G>A NP_001394595.1:p.Cys1210Tyr missense NM_001407667.1:c.3629G>A NP_001394596.1:p.Cys1210Tyr missense NM_001407668.1:c.3629G>A NP_001394597.1:p.Cys1210Tyr missense NM_001407669.1:c.3629G>A NP_001394598.1:p.Cys1210Tyr missense NM_001407670.1:c.3626G>A NP_001394599.1:p.Cys1209Tyr missense NM_001407671.1:c.3626G>A NP_001394600.1:p.Cys1209Tyr missense NM_001407672.1:c.3626G>A NP_001394601.1:p.Cys1209Tyr missense NM_001407673.1:c.3626G>A NP_001394602.1:p.Cys1209Tyr missense NM_001407674.1:c.3629G>A NP_001394603.1:p.Cys1210Tyr missense NM_001407675.1:c.3629G>A NP_001394604.1:p.Cys1210Tyr missense NM_001407676.1:c.3629G>A NP_001394605.1:p.Cys1210Tyr missense NM_001407677.1:c.3629G>A NP_001394606.1:p.Cys1210Tyr missense NM_001407678.1:c.3629G>A NP_001394607.1:p.Cys1210Tyr missense NM_001407679.1:c.3629G>A NP_001394608.1:p.Cys1210Tyr missense NM_001407680.1:c.3629G>A NP_001394609.1:p.Cys1210Tyr missense NM_001407681.1:c.3629G>A NP_001394610.1:p.Cys1210Tyr missense NM_001407682.1:c.3629G>A NP_001394611.1:p.Cys1210Tyr missense NM_001407683.1:c.3629G>A NP_001394612.1:p.Cys1210Tyr missense NM_001407684.1:c.3752G>A NP_001394613.1:p.Cys1251Tyr missense NM_001407685.1:c.3626G>A NP_001394614.1:p.Cys1209Tyr missense NM_001407686.1:c.3626G>A NP_001394615.1:p.Cys1209Tyr missense NM_001407687.1:c.3626G>A NP_001394616.1:p.Cys1209Tyr missense NM_001407688.1:c.3626G>A NP_001394617.1:p.Cys1209Tyr missense NM_001407689.1:c.3626G>A NP_001394618.1:p.Cys1209Tyr missense NM_001407690.1:c.3626G>A NP_001394619.1:p.Cys1209Tyr missense NM_001407691.1:c.3626G>A NP_001394620.1:p.Cys1209Tyr missense NM_001407692.1:c.3611G>A NP_001394621.1:p.Cys1204Tyr missense NM_001407694.1:c.3611G>A NP_001394623.1:p.Cys1204Tyr missense NM_001407695.1:c.3611G>A NP_001394624.1:p.Cys1204Tyr missense NM_001407696.1:c.3611G>A NP_001394625.1:p.Cys1204Tyr missense NM_001407697.1:c.3611G>A NP_001394626.1:p.Cys1204Tyr missense NM_001407698.1:c.3611G>A NP_001394627.1:p.Cys1204Tyr missense NM_001407724.1:c.3611G>A NP_001394653.1:p.Cys1204Tyr missense NM_001407725.1:c.3611G>A NP_001394654.1:p.Cys1204Tyr missense NM_001407726.1:c.3611G>A NP_001394655.1:p.Cys1204Tyr missense NM_001407727.1:c.3611G>A NP_001394656.1:p.Cys1204Tyr missense NM_001407728.1:c.3611G>A NP_001394657.1:p.Cys1204Tyr missense NM_001407729.1:c.3611G>A NP_001394658.1:p.Cys1204Tyr missense NM_001407730.1:c.3611G>A NP_001394659.1:p.Cys1204Tyr missense NM_001407731.1:c.3611G>A NP_001394660.1:p.Cys1204Tyr missense NM_001407732.1:c.3611G>A NP_001394661.1:p.Cys1204Tyr missense NM_001407733.1:c.3611G>A NP_001394662.1:p.Cys1204Tyr missense NM_001407734.1:c.3611G>A NP_001394663.1:p.Cys1204Tyr missense NM_001407735.1:c.3611G>A NP_001394664.1:p.Cys1204Tyr missense NM_001407736.1:c.3611G>A NP_001394665.1:p.Cys1204Tyr missense NM_001407737.1:c.3611G>A NP_001394666.1:p.Cys1204Tyr missense NM_001407738.1:c.3611G>A NP_001394667.1:p.Cys1204Tyr missense NM_001407739.1:c.3611G>A NP_001394668.1:p.Cys1204Tyr missense NM_001407740.1:c.3608G>A NP_001394669.1:p.Cys1203Tyr missense NM_001407741.1:c.3608G>A NP_001394670.1:p.Cys1203Tyr missense NM_001407742.1:c.3608G>A NP_001394671.1:p.Cys1203Tyr missense NM_001407743.1:c.3608G>A NP_001394672.1:p.Cys1203Tyr missense NM_001407744.1:c.3608G>A NP_001394673.1:p.Cys1203Tyr missense NM_001407745.1:c.3608G>A NP_001394674.1:p.Cys1203Tyr missense NM_001407746.1:c.3608G>A NP_001394675.1:p.Cys1203Tyr missense NM_001407747.1:c.3608G>A NP_001394676.1:p.Cys1203Tyr missense NM_001407748.1:c.3608G>A NP_001394677.1:p.Cys1203Tyr missense NM_001407749.1:c.3608G>A NP_001394678.1:p.Cys1203Tyr missense NM_001407750.1:c.3611G>A NP_001394679.1:p.Cys1204Tyr missense NM_001407751.1:c.3611G>A NP_001394680.1:p.Cys1204Tyr missense NM_001407752.1:c.3611G>A NP_001394681.1:p.Cys1204Tyr missense NM_001407838.1:c.3608G>A NP_001394767.1:p.Cys1203Tyr missense NM_001407839.1:c.3608G>A NP_001394768.1:p.Cys1203Tyr missense NM_001407841.1:c.3608G>A NP_001394770.1:p.Cys1203Tyr missense NM_001407842.1:c.3608G>A NP_001394771.1:p.Cys1203Tyr missense NM_001407843.1:c.3608G>A NP_001394772.1:p.Cys1203Tyr missense NM_001407844.1:c.3608G>A NP_001394773.1:p.Cys1203Tyr missense NM_001407845.1:c.3608G>A NP_001394774.1:p.Cys1203Tyr missense NM_001407846.1:c.3608G>A NP_001394775.1:p.Cys1203Tyr missense NM_001407847.1:c.3608G>A NP_001394776.1:p.Cys1203Tyr missense NM_001407848.1:c.3608G>A NP_001394777.1:p.Cys1203Tyr missense NM_001407849.1:c.3608G>A NP_001394778.1:p.Cys1203Tyr missense NM_001407850.1:c.3611G>A NP_001394779.1:p.Cys1204Tyr missense NM_001407851.1:c.3611G>A NP_001394780.1:p.Cys1204Tyr missense NM_001407852.1:c.3611G>A NP_001394781.1:p.Cys1204Tyr missense NM_001407853.1:c.3539G>A NP_001394782.1:p.Cys1180Tyr missense NM_001407854.1:c.3752G>A NP_001394783.1:p.Cys1251Tyr missense NM_001407858.1:c.3752G>A NP_001394787.1:p.Cys1251Tyr missense NM_001407859.1:c.3752G>A NP_001394788.1:p.Cys1251Tyr missense NM_001407860.1:c.3749G>A NP_001394789.1:p.Cys1250Tyr missense NM_001407861.1:c.3749G>A NP_001394790.1:p.Cys1250Tyr missense NM_001407862.1:c.3551G>A NP_001394791.1:p.Cys1184Tyr missense NM_001407863.1:c.3629G>A NP_001394792.1:p.Cys1210Tyr missense NM_001407874.1:c.3548G>A NP_001394803.1:p.Cys1183Tyr missense NM_001407875.1:c.3548G>A NP_001394804.1:p.Cys1183Tyr missense NM_001407879.1:c.3542G>A NP_001394808.1:p.Cys1181Tyr missense NM_001407881.1:c.3542G>A NP_001394810.1:p.Cys1181Tyr missense NM_001407882.1:c.3542G>A NP_001394811.1:p.Cys1181Tyr missense NM_001407884.1:c.3542G>A NP_001394813.1:p.Cys1181Tyr missense NM_001407885.1:c.3542G>A NP_001394814.1:p.Cys1181Tyr missense NM_001407886.1:c.3542G>A NP_001394815.1:p.Cys1181Tyr missense NM_001407887.1:c.3542G>A NP_001394816.1:p.Cys1181Tyr missense NM_001407889.1:c.3542G>A NP_001394818.1:p.Cys1181Tyr missense NM_001407894.1:c.3539G>A NP_001394823.1:p.Cys1180Tyr missense NM_001407895.1:c.3539G>A NP_001394824.1:p.Cys1180Tyr missense NM_001407896.1:c.3539G>A NP_001394825.1:p.Cys1180Tyr missense NM_001407897.1:c.3539G>A NP_001394826.1:p.Cys1180Tyr missense NM_001407898.1:c.3539G>A NP_001394827.1:p.Cys1180Tyr missense NM_001407899.1:c.3539G>A NP_001394828.1:p.Cys1180Tyr missense NM_001407900.1:c.3542G>A NP_001394829.1:p.Cys1181Tyr missense NM_001407902.1:c.3542G>A NP_001394831.1:p.Cys1181Tyr missense NM_001407904.1:c.3542G>A NP_001394833.1:p.Cys1181Tyr missense NM_001407906.1:c.3542G>A NP_001394835.1:p.Cys1181Tyr missense NM_001407907.1:c.3542G>A NP_001394836.1:p.Cys1181Tyr missense NM_001407908.1:c.3542G>A NP_001394837.1:p.Cys1181Tyr missense NM_001407909.1:c.3542G>A NP_001394838.1:p.Cys1181Tyr missense NM_001407910.1:c.3542G>A NP_001394839.1:p.Cys1181Tyr missense NM_001407915.1:c.3539G>A NP_001394844.1:p.Cys1180Tyr missense NM_001407916.1:c.3539G>A NP_001394845.1:p.Cys1180Tyr missense NM_001407917.1:c.3539G>A NP_001394846.1:p.Cys1180Tyr missense NM_001407918.1:c.3539G>A NP_001394847.1:p.Cys1180Tyr missense NM_001407919.1:c.3629G>A NP_001394848.1:p.Cys1210Tyr missense NM_001407920.1:c.3488G>A NP_001394849.1:p.Cys1163Tyr missense NM_001407921.1:c.3488G>A NP_001394850.1:p.Cys1163Tyr missense NM_001407922.1:c.3488G>A NP_001394851.1:p.Cys1163Tyr missense NM_001407923.1:c.3488G>A NP_001394852.1:p.Cys1163Tyr missense NM_001407924.1:c.3488G>A NP_001394853.1:p.Cys1163Tyr missense NM_001407925.1:c.3488G>A NP_001394854.1:p.Cys1163Tyr missense NM_001407926.1:c.3488G>A NP_001394855.1:p.Cys1163Tyr missense NM_001407927.1:c.3488G>A NP_001394856.1:p.Cys1163Tyr missense NM_001407928.1:c.3488G>A NP_001394857.1:p.Cys1163Tyr missense NM_001407929.1:c.3488G>A NP_001394858.1:p.Cys1163Tyr missense NM_001407930.1:c.3485G>A NP_001394859.1:p.Cys1162Tyr missense NM_001407931.1:c.3485G>A NP_001394860.1:p.Cys1162Tyr missense NM_001407932.1:c.3485G>A NP_001394861.1:p.Cys1162Tyr missense NM_001407933.1:c.3488G>A NP_001394862.1:p.Cys1163Tyr missense NM_001407934.1:c.3485G>A NP_001394863.1:p.Cys1162Tyr missense NM_001407935.1:c.3488G>A NP_001394864.1:p.Cys1163Tyr missense NM_001407936.1:c.3485G>A NP_001394865.1:p.Cys1162Tyr missense NM_001407937.1:c.3629G>A NP_001394866.1:p.Cys1210Tyr missense NM_001407938.1:c.3629G>A NP_001394867.1:p.Cys1210Tyr missense NM_001407939.1:c.3629G>A NP_001394868.1:p.Cys1210Tyr missense NM_001407940.1:c.3626G>A NP_001394869.1:p.Cys1209Tyr missense NM_001407941.1:c.3626G>A NP_001394870.1:p.Cys1209Tyr missense NM_001407942.1:c.3611G>A NP_001394871.1:p.Cys1204Tyr missense NM_001407943.1:c.3608G>A NP_001394872.1:p.Cys1203Tyr missense NM_001407944.1:c.3611G>A NP_001394873.1:p.Cys1204Tyr missense NM_001407945.1:c.3611G>A NP_001394874.1:p.Cys1204Tyr missense NM_001407946.1:c.3419G>A NP_001394875.1:p.Cys1140Tyr missense NM_001407947.1:c.3419G>A NP_001394876.1:p.Cys1140Tyr missense NM_001407948.1:c.3419G>A NP_001394877.1:p.Cys1140Tyr missense NM_001407949.1:c.3419G>A NP_001394878.1:p.Cys1140Tyr missense NM_001407950.1:c.3419G>A NP_001394879.1:p.Cys1140Tyr missense NM_001407951.1:c.3419G>A NP_001394880.1:p.Cys1140Tyr missense NM_001407952.1:c.3419G>A NP_001394881.1:p.Cys1140Tyr missense NM_001407953.1:c.3419G>A NP_001394882.1:p.Cys1140Tyr missense NM_001407954.1:c.3416G>A NP_001394883.1:p.Cys1139Tyr missense NM_001407955.1:c.3416G>A NP_001394884.1:p.Cys1139Tyr missense NM_001407956.1:c.3416G>A NP_001394885.1:p.Cys1139Tyr missense NM_001407957.1:c.3419G>A NP_001394886.1:p.Cys1140Tyr missense NM_001407958.1:c.3416G>A NP_001394887.1:p.Cys1139Tyr missense NM_001407959.1:c.3371G>A NP_001394888.1:p.Cys1124Tyr missense NM_001407960.1:c.3371G>A NP_001394889.1:p.Cys1124Tyr missense NM_001407962.1:c.3368G>A NP_001394891.1:p.Cys1123Tyr missense NM_001407963.1:c.3371G>A NP_001394892.1:p.Cys1124Tyr missense NM_001407964.1:c.3608G>A NP_001394893.1:p.Cys1203Tyr missense NM_001407965.1:c.3248G>A NP_001394894.1:p.Cys1083Tyr missense NM_001407966.1:c.2864G>A NP_001394895.1:p.Cys955Tyr missense NM_001407967.1:c.2864G>A NP_001394896.1:p.Cys955Tyr missense NM_001407968.1:c.1148G>A NP_001394897.1:p.Cys383Tyr missense NM_001407969.1:c.1148G>A NP_001394898.1:p.Cys383Tyr missense NM_001407970.1:c.788-747G>A intron variant NM_001407971.1:c.788-747G>A intron variant NM_001407972.1:c.785-747G>A intron variant NM_001407973.1:c.788-747G>A intron variant NM_001407974.1:c.788-747G>A intron variant NM_001407975.1:c.788-747G>A intron variant NM_001407976.1:c.788-747G>A intron variant NM_001407977.1:c.788-747G>A intron variant NM_001407978.1:c.788-747G>A intron variant NM_001407979.1:c.788-747G>A intron variant NM_001407980.1:c.788-747G>A intron variant NM_001407981.1:c.788-747G>A intron variant NM_001407982.1:c.788-747G>A intron variant NM_001407983.1:c.788-747G>A intron variant NM_001407984.1:c.785-747G>A intron variant NM_001407985.1:c.785-747G>A intron variant NM_001407986.1:c.785-747G>A intron variant NM_001407990.1:c.788-747G>A intron variant NM_001407991.1:c.785-747G>A intron variant NM_001407992.1:c.785-747G>A intron variant NM_001407993.1:c.788-747G>A intron variant NM_001408392.1:c.785-747G>A intron variant NM_001408396.1:c.785-747G>A intron variant NM_001408397.1:c.785-747G>A intron variant NM_001408398.1:c.785-747G>A intron variant NM_001408399.1:c.785-747G>A intron variant NM_001408400.1:c.785-747G>A intron variant NM_001408401.1:c.785-747G>A intron variant NM_001408402.1:c.785-747G>A intron variant NM_001408403.1:c.788-747G>A intron variant NM_001408404.1:c.788-747G>A intron variant NM_001408406.1:c.791-756G>A intron variant NM_001408407.1:c.785-747G>A intron variant NM_001408408.1:c.779-747G>A intron variant NM_001408409.1:c.710-747G>A intron variant NM_001408410.1:c.647-747G>A intron variant NM_001408411.1:c.710-747G>A intron variant NM_001408412.1:c.710-747G>A intron variant NM_001408413.1:c.707-747G>A intron variant NM_001408414.1:c.710-747G>A intron variant NM_001408415.1:c.710-747G>A intron variant NM_001408416.1:c.707-747G>A intron variant NM_001408418.1:c.671-747G>A intron variant NM_001408419.1:c.671-747G>A intron variant NM_001408420.1:c.671-747G>A intron variant NM_001408421.1:c.668-747G>A intron variant NM_001408422.1:c.671-747G>A intron variant NM_001408423.1:c.671-747G>A intron variant NM_001408424.1:c.668-747G>A intron variant NM_001408425.1:c.665-747G>A intron variant NM_001408426.1:c.665-747G>A intron variant NM_001408427.1:c.665-747G>A intron variant NM_001408428.1:c.665-747G>A intron variant NM_001408429.1:c.665-747G>A intron variant NM_001408430.1:c.665-747G>A intron variant NM_001408431.1:c.668-747G>A intron variant NM_001408432.1:c.662-747G>A intron variant NM_001408433.1:c.662-747G>A intron variant NM_001408434.1:c.662-747G>A intron variant NM_001408435.1:c.662-747G>A intron variant NM_001408436.1:c.665-747G>A intron variant NM_001408437.1:c.665-747G>A intron variant NM_001408438.1:c.665-747G>A intron variant NM_001408439.1:c.665-747G>A intron variant NM_001408440.1:c.665-747G>A intron variant NM_001408441.1:c.665-747G>A intron variant NM_001408442.1:c.665-747G>A intron variant NM_001408443.1:c.665-747G>A intron variant NM_001408444.1:c.665-747G>A intron variant NM_001408445.1:c.662-747G>A intron variant NM_001408446.1:c.662-747G>A intron variant NM_001408447.1:c.662-747G>A intron variant NM_001408448.1:c.662-747G>A intron variant NM_001408450.1:c.662-747G>A intron variant NM_001408451.1:c.653-747G>A intron variant NM_001408452.1:c.647-747G>A intron variant NM_001408453.1:c.647-747G>A intron variant NM_001408454.1:c.647-747G>A intron variant NM_001408455.1:c.647-747G>A intron variant NM_001408456.1:c.647-747G>A intron variant NM_001408457.1:c.647-747G>A intron variant NM_001408458.1:c.647-747G>A intron variant NM_001408459.1:c.647-747G>A intron variant NM_001408460.1:c.647-747G>A intron variant NM_001408461.1:c.647-747G>A intron variant NM_001408462.1:c.644-747G>A intron variant NM_001408463.1:c.644-747G>A intron variant NM_001408464.1:c.644-747G>A intron variant NM_001408465.1:c.644-747G>A intron variant NM_001408466.1:c.647-747G>A intron variant NM_001408467.1:c.647-747G>A intron variant NM_001408468.1:c.644-747G>A intron variant NM_001408469.1:c.647-747G>A intron variant NM_001408470.1:c.644-747G>A intron variant NM_001408472.1:c.788-747G>A intron variant NM_001408473.1:c.785-747G>A intron variant NM_001408474.1:c.587-747G>A intron variant NM_001408475.1:c.584-747G>A intron variant NM_001408476.1:c.587-747G>A intron variant NM_001408478.1:c.578-747G>A intron variant NM_001408479.1:c.578-747G>A intron variant NM_001408480.1:c.578-747G>A intron variant NM_001408481.1:c.578-747G>A intron variant NM_001408482.1:c.578-747G>A intron variant NM_001408483.1:c.578-747G>A intron variant NM_001408484.1:c.578-747G>A intron variant NM_001408485.1:c.578-747G>A intron variant NM_001408489.1:c.578-747G>A intron variant NM_001408490.1:c.575-747G>A intron variant NM_001408491.1:c.575-747G>A intron variant NM_001408492.1:c.578-747G>A intron variant NM_001408493.1:c.575-747G>A intron variant NM_001408494.1:c.548-747G>A intron variant NM_001408495.1:c.545-747G>A intron variant NM_001408496.1:c.524-747G>A intron variant NM_001408497.1:c.524-747G>A intron variant NM_001408498.1:c.524-747G>A intron variant NM_001408499.1:c.524-747G>A intron variant NM_001408500.1:c.524-747G>A intron variant NM_001408501.1:c.524-747G>A intron variant NM_001408502.1:c.455-747G>A intron variant NM_001408503.1:c.521-747G>A intron variant NM_001408504.1:c.521-747G>A intron variant NM_001408505.1:c.521-747G>A intron variant NM_001408506.1:c.461-747G>A intron variant NM_001408507.1:c.461-747G>A intron variant NM_001408508.1:c.452-747G>A intron variant NM_001408509.1:c.452-747G>A intron variant NM_001408510.1:c.407-747G>A intron variant NM_001408511.1:c.404-747G>A intron variant NM_001408512.1:c.284-747G>A intron variant NM_001408513.1:c.578-747G>A intron variant NM_001408514.1:c.578-747G>A intron variant NM_007297.4:c.3611G>A NP_009228.2:p.Cys1204Tyr missense NM_007298.4:c.788-747G>A intron variant NM_007299.4:c.788-747G>A intron variant NM_007300.4:c.3752G>A NP_009231.2:p.Cys1251Tyr missense NR_027676.1:n.3888G>A NC_000017.11:g.43091779C>T NC_000017.10:g.41243796C>T NG_005905.2:g.126205G>A NG_087068.1:g.761C>T LRG_292:g.126205G>A LRG_292t1:c.3752G>A LRG_292p1:p.Cys1251Tyr - Protein change
- C1251Y, C1204Y, C1140Y, C1124Y, C1139Y, C1162Y, C1181Y, C1203Y, C1210Y, C1248Y, C1250Y, C1083Y, C1123Y, C1180Y, C1209Y, C1225Y, C383Y, C955Y, C1163Y, C1183Y, C1184Y, C1224Y
- Other names
- -
- Canonical SPDI
- NC_000017.11:43091778:C:T
-
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 |
13044 | 14850 | |
| 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 (1) |
criteria provided, single submitter
|
Nov 3, 2015 | RCV000236428.2 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Mar 23, 2023 | RCV003157490.4 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 16, 2022 | RCV002519825.3 |
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
(Nov 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000293383.10
First in ClinVar: Jul 25, 2016 Last updated: Jul 25, 2016 |
Comment:
This variant is denoted BRCA1 c.3752G>A at the cDNA level, p.Cys1251Tyr (C1251Y) at the protein level, and results in the change of a Cysteine to … (more)
This variant is denoted BRCA1 c.3752G>A at the cDNA level, p.Cys1251Tyr (C1251Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGT>TAT). Using alternate nomenclature, this variant would be defined as BRCA1 3871G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Cys1251Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Cysteine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Cys1251Tyr occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Cys1251Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
|
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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: SCV003849752.1
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
(Dec 20, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004360218.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces cysteine with tyrosine at codon 1251 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces cysteine with tyrosine at codon 1251 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial breast cancer (PMID: 34287479). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
|
Uncertain significance
(Jan 16, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003020956.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 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: 246072). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1251 of the BRCA1 protein (p.Cys1251Tyr). (less)
|
Comment:
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This missense variant replaces cysteine with tyrosine at codon 1251 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial breast cancer (PMID: 34287479). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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: 246072). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1251 of the BRCA1 protein (p.Cys1251Tyr).
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:
This variant is denoted BRCA1 c.3752G>A at the cDNA level, p.Cys1251Tyr (C1251Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGT>TAT). Using alternate nomenclature, this variant would be defined as BRCA1 3871G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Cys1251Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Cysteine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Cys1251Tyr occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Cys1251Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This missense variant replaces cysteine with tyrosine at codon 1251 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial breast cancer (PMID: 34287479). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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: 246072). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1251 of the BRCA1 protein (p.Cys1251Tyr).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Germline and Somatic mutations in postmenopausal breast cancer patients. | Nagy TR | Clinics (Sao Paulo, Brazil) | 2021 | PMID: 34287479 |
| 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 |
Text-mined citations for rs879254079 ...
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Record last updated Sep 29, 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.