ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.441+17T>C (rs368415464)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159864 SCV000209912 benign not specified 2014-08-26 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.
Invitae RCV000199466 SCV000253503 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000409577 SCV000488991 likely benign Breast-ovarian cancer, familial 1 2016-07-29 criteria provided, single submitter clinical testing
Color RCV000581016 SCV000683180 likely benign Hereditary cancer-predisposing syndrome 2017-04-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000159864 SCV000699144 benign not specified 2019-12-19 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.441+17T>C 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 was absent in 246020 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.441+17T>C has not been reported in individuals affected with Hereditary Breast and Ovarian Cancer, however has been reported in one healthy individual, age not specified (Meghani 2016). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variants have been reported in our internal database (BRCA2 c.9253dupA, p.Thr3085fsX26; CHEK2 c.1100delC, p.Thr367fsX15; BRCA1 c.3340G>T, p.Glu1114X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitter (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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