ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4485-10A>G (rs863224420)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197772 SCV000253505 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000579627 SCV000683189 likely benign Hereditary cancer-predisposing syndrome 2016-07-11 criteria provided, single submitter clinical testing
GeneDx RCV000758831 SCV000720717 likely benign not provided 2021-05-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758831 SCV000887698 likely benign not provided 2017-11-24 criteria provided, single submitter clinical testing
Mendelics RCV000989881 SCV001140519 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Liquid Biopsy and Precision Medicine Group,Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research RCV001090204 SCV001245502 uncertain significance Familial cancer of breast criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000599872 SCV001478708 likely benign not specified 2021-01-10 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4485-10A>G 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. This is supported by functional studies that report no impact of this variant on mRNA splicing and no abnormal transcripts detected by in vitro RNA analysis (Montalban_2019). The variant allele was found at a frequency of 1.2e-05 in 250790 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4485-10A>G has been reported in the literature in one study reporting the mutational spectrum of BRCA1 and BRCA2 genes among hereditary breast cancer families in Chile (Alvarez_2017). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six 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=1)/likely benign (n=5). Based on the evidence outlined above reflecting the emerging consensus, the variant was classified as likely benign.
Hereditary Cancer Genetics group,Vall d'Hebron Institute of Oncology RCV000197772 SCV000916352 benign Hereditary breast and ovarian cancer syndrome 2019-03-01 no assertion criteria provided research

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