ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5304C>T (p.Cys1768=) (rs138493864)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495218 SCV000578387 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000159892 SCV000209989 benign not specified 2014-04-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000163518 SCV000214076 likely benign Hereditary cancer-predisposing syndrome 2014-10-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001086394 SCV000253514 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163518 SCV000683285 likely benign Hereditary cancer-predisposing syndrome 2016-06-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000159892 SCV000699235 benign not specified 2019-03-08 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5304C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.6e-05 in 277382 control chromosomes, predominantly at a frequency of 0.00042 within the African subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (3.6e-05 vs 0.001). This variant has been reported in the literature in one individual affected with Breast and Ovarian Cancer (Suter_2004). This variant has also been reported in 3/9884 women who are older than age 70 and cancer free, suggesting this variant does not associate with cancer. One publication reports experimental evidence evaluating an impact on protein function and showed this variant had normal function (Findlay_2018). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Counsyl RCV000495218 SCV000786180 likely benign Breast-ovarian cancer, familial 1 2018-03-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590732 SCV000887718 likely benign not provided 2018-07-11 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287683 SCV001474395 likely benign none provided 2019-08-01 criteria provided, single submitter clinical testing
Brotman Baty Institute,University of Washington RCV000495218 SCV001238100 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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