Submissions for variant NM_007294.4(BRCA1):c.3012G>A (p.Glu1004=)

gnomAD frequency: 0.00002  dbSNP: rs786201784

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000494859	SCV000578257	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics	RCV000164252	SCV000214876	likely benign	Hereditary cancer-predisposing syndrome	2015-02-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000589951	SCV000224998	uncertain significance	not provided	2015-01-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226901	SCV000289769	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000589951	SCV000321425	uncertain significance	not provided	2016-03-04	criteria provided, single submitter	clinical testing	This variant is denoted BRCA1 c.3012G>A at the DNA level. This variant is silent at the coding level, preserving a Glutamic Acid at codon 1004. Using alternate nomenclature, this variant would be defined as BRCA1 3131G>A. It is not predicted to cause abnormal splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 c.3012G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The nucleotide which is altered, a guanine (G) at base 3012, is conserved in mammals. Based on currently available information, it is unclear whether BRCA1 c.3012G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000855612	SCV000698997	likely benign	not specified	2019-08-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589951	SCV000887655	likely benign	not provided	2022-06-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164252	SCV000909325	likely benign	Hereditary cancer-predisposing syndrome	2018-08-14	criteria provided, single submitter	clinical testing
Mendelics	RCV000494859	SCV001140566	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164252	SCV002538170	likely benign	Hereditary cancer-predisposing syndrome	2021-10-08	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV004554731	SCV004746477	likely benign	BRCA1-related disorder	2019-03-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).