Submissions for variant NM_007294.4(BRCA1):c.81-12C>G

gnomAD frequency: 0.00066  dbSNP: rs80358055

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000589396	SCV000210059	likely benign	not provided	2021-05-04	criteria provided, single submitter	clinical testing	In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 21523855, 15829246, 16267036, 30209399)
Counsyl	RCV000077183	SCV000220999	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-12-30	criteria provided, single submitter	literature only
Invitae	RCV001081745	SCV000252824	benign	Hereditary breast ovarian cancer syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580482	SCV000683362	likely benign	Hereditary cancer-predisposing syndrome	2015-03-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589396	SCV000699306	benign	not provided	2016-05-31	criteria provided, single submitter	clinical testing	Variant Summary: This intronic mutation involves the alteration of a nucleotide in the -12 position of intron 3 of BRCA1. The variant is present in the control population at a frequency of 0.03%, but is almost exclusively found in the African subpopulation, with a frequency of 0.3% This frequency is 3-fold the maximal expected allele frequency for a pathogenic variant in BRCA1, which is strong evidence that this is a benign polymorphism present mainly in populatons of African origin. This variant was also observed in trans with a known deleterious BRCA1 variant, further evidence of the benign nature of the variant. Multiple reputable clinical labs/databases have classified the variant as likely benign/benign. In additiona, 5/5 in silico tools via Alamut predict an impact on splicing as do prediction tools used in Mucaki_2011 however these findings have not been supported by functional studies. Taken together, this variant has been classified as benign.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001081745	SCV002026044	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580482	SCV002537909	benign	Hereditary cancer-predisposing syndrome	2021-03-02	criteria provided, single submitter	curation
Sharing Clinical Reports Project (SCRP)	RCV000077183	SCV000108980	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2009-12-10	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077183	SCV000144217	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Brotman Baty Institute, University of Washington	RCV000077183	SCV001241833	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro