ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5278-20C>T (rs193149108)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426671 SCV000515691 likely benign not specified 2017-07-13 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 RCV000465391 SCV000560293 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000662703 SCV000785450 likely benign Breast-ovarian cancer, familial 1 2017-08-11 criteria provided, single submitter clinical testing
Color RCV000771434 SCV000903799 likely benign Hereditary cancer-predisposing syndrome 2015-12-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000426671 SCV001360672 uncertain significance not specified 2019-10-17 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5278-20C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 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 3.9e-05 in 282250 control chromosomes, predominantly at a frequency of 0.00044 within the African or African-American 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 (0.00044 vs 0.001), allowing no conclusion about variant significance. To our knowledge, there are no reports of c.5278-20C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating an impact on protein function in the literature. Four ClinVar submissions (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Brotman Baty Institute,University of Washington RCV000662703 SCV001238042 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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