ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5412C>T (p.Val1804=) (rs730881456)

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Total submissions: 9
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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) RCV000411366 SCV000578334 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 RCV000159893 SCV000209993 benign not specified 2014-09-26 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 RCV000162643 SCV000213080 likely benign Hereditary cancer-predisposing syndrome 2014-10-13 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.
Counsyl RCV000411366 SCV000488566 likely benign Breast-ovarian cancer, familial 1 2016-05-09 criteria provided, single submitter clinical testing
Invitae RCV001080425 SCV000560260 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162643 SCV000683312 likely benign Hereditary cancer-predisposing syndrome 2016-11-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000159893 SCV000699252 benign not specified 2019-03-15 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5412C>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 1.8e-05 in 277420 control chromosomes (gnomAD and controls from the publication). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. This variant has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. The variant has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer, typically classified by the authors as a benign or a variant of unknown clinical significance (Judkins_2005, McKean-Cowdin_2005, Caux-Moncoutier_2011, Minucci_2015, Msolly_2015). In one study, the variant was identified within two independent families and did not cosegregate with disease, suggesting a benign impact for this variant (McKean-Cowdin_2005). At least one publication reports experimental evidence evaluating an impact on protein function (Findlay_2018). These results showed no damaging effect of this variant. Five 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589790 SCV000888946 likely benign not provided 2019-04-17 criteria provided, single submitter clinical testing
Brotman Baty Institute,University of Washington RCV000411366 SCV001238358 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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