Submissions for variant NM_007294.4(BRCA1):c.301+8T>C

gnomAD frequency: 0.00054  dbSNP: rs80358101

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112243	SCV001161571	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-06-18	reviewed by expert panel	curation	Variant allele has no predicted coding change (intronic variant), AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/), AND minor allele frequency 0.00148 (African), derived from gnomAD v2.1.1 non-cancer (2019-05-13).
GeneDx	RCV000123880	SCV000167225	benign	not specified	2014-03-14	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.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000112243	SCV000195880	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083641	SCV000252815	benign	Hereditary breast ovarian cancer syndrome	2025-02-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580640	SCV000683079	likely benign	Hereditary cancer-predisposing syndrome	2016-05-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586430	SCV000698995	likely benign	not provided	2016-03-24	criteria provided, single submitter	clinical testing	Variant summary: c.301+8T>C affects a non-conserved nucleotide, resulting in an intronic change. Mutation taster predicts benign outcome. The variant is located in a position not widely known to affect splicing and 5/5 splicing prediction programs suggest no effect on splicing. This variant was found in 17/121300 control chromosomes at a frequency of 0.0001401, predominantly observed in the African subpopulation of ExAC with observed MAF of 0.001252, which exceeds the maximal expected frequency of a pathogenic allele (0.0010005), suggesting that the variant might be a polymorphism found in population(s) of African origin. Although the variant has been reported in subjects from HBOC families, there is no cosegregation study to show whether the variant could have explained the phenotype. BIC cites variant in one individual who also carried a potentially pathogenic variant BRCA1 c.302-1G>A. In addition, multiple clinical laboratories classified this variant as benign. Considering all, this variant is classified as Likely Benign until more information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586430	SCV000888883	benign	not provided	2022-10-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000112243	SCV001285181	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001083641	SCV002026033	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586430	SCV002049102	likely benign	not provided	2024-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV001083641	SCV002515231	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000580640	SCV002538169	likely benign	Hereditary cancer-predisposing syndrome	2021-07-30	criteria provided, single submitter	curation
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112243	SCV000144959	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000112243	SCV000297596	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2012-11-30	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000586430	SCV000591256	likely benign	not provided		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000586430	SCV000778778	likely benign	not provided	2017-11-01	no assertion criteria provided	clinical testing
Brotman Baty Institute, University of Washington	RCV000112243	SCV001243163	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Genetic Services Laboratory, University of Chicago	RCV000123880	SCV003839264	likely benign	not specified	2022-04-20	no assertion criteria provided	clinical testing