ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5075-9A>T (rs80358059)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000112490 SCV000220675 likely benign Breast-ovarian cancer, familial 1 2014-09-07 criteria provided, single submitter literature only
Invitae RCV000200150 SCV000252819 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV001284298 SCV000518084 likely benign not provided 2020-11-30 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21990134, 29750258, 16267036, 22505045, 26913838, 17924331, 30209399)
Color Health, Inc RCV000582773 SCV000688536 benign Hereditary cancer-predisposing syndrome 2017-09-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000426508 SCV001338187 benign not specified 2020-02-24 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5075-9A>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. 4/4 computational tools predict no significant impact on normal splicing. The variant allele was found at a frequency of 8e-06 in 250922 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5075-9A>T has been reported in the literature in studies of individuals affected with Hereditary Breast and Ovarian Cancer, in studies evaluating multifactorial and posterior probability models to assess variant pathogenicity, in splicing studies using PAX gene collection systems and as a training set for evaluating a new prediction protocol aimed at spliceogenic variants (example, Judkins_2005, Easton_2007, Lindor_2012, Houdayer_2012, Leman_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At-least one co-occurrence with another pathogenic variant has been reported in the BIC database (BRCA1 c.1999C>T, p.Gln667*), providing additional supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on splicing. These results showed no damaging effect of this variant on splicing (Houdayer_2012)(class 1S). Three 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 benign (n=2)/likely benign (n=1). Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284298 SCV001470008 likely benign not provided 2019-12-29 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112490 SCV000145301 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000112490 SCV001237552 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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