ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4269C>T (p.Ser1423=) (rs786202278)

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Total submissions: 6
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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) RCV000495645 SCV000578079 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/).
Ambry Genetics RCV000165008 SCV000215703 likely benign Hereditary cancer-predisposing syndrome 2014-12-24 criteria provided, single submitter clinical testing
GeneDx RCV000423675 SCV000520382 likely benign not specified 2016-11-29 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.
Invitae RCV000550924 SCV000635961 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-09 criteria provided, single submitter clinical testing
Color RCV000165008 SCV000683169 likely benign Hereditary cancer-predisposing syndrome 2015-12-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000423675 SCV000918782 uncertain significance not specified 2018-10-15 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4269C>T results 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 was absent in 246218 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4269C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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