ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4113G>A (p.Gly1371=) (rs147448807)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495241 SCV000578224 likely benign Breast-ovarian cancer, familial 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/).
GeneDx RCV000174120 SCV000167300 benign not specified 2014-02-25 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.
Ambry Genetics RCV000162559 SCV000212969 likely benign Hereditary cancer-predisposing syndrome 2014-06-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174120 SCV000225365 likely benign not specified 2014-09-26 criteria provided, single submitter clinical testing
Invitae RCV000198974 SCV000252816 benign Hereditary breast and ovarian cancer syndrome 2020-11-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV000460094 SCV000540980 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283018 SCV000602718 likely benign none provided 2020-06-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162559 SCV000683151 likely benign Hereditary cancer-predisposing syndrome 2015-07-28 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000174120 SCV000806943 benign not specified 2017-07-14 criteria provided, single submitter clinical testing
Mendelics RCV000495241 SCV001140536 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000495241 SCV001283851 likely benign Breast-ovarian cancer, familial 1 2017-12-06 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001200222 SCV001371125 likely benign not provided 2020-05-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353654 SCV000591490 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Gly1371Gly variant was identified in 1 of 158 proband chromosomes (frequency: 0.006) from individuals or families with breast and colon cancer, and was not identified in 200 control chromosomes from healthy individuals (Cherbal 2012). The variant was also previously identified by our laboratory in 1 individual with breast cancer. The variant was identified in dbSNP (ID: rs147448807), with a minor allele frequency of 0.0016 (1000 Genomes Project), NHLBI GO Exome Sequencing Project in 16 of 4406 alleles (freq.0.004). The variant was identified in the Exome Aggregation Consortium database (March 14, 2016) in 50 of 99796 chromosomes (freq. 0.000501) in the following populations: African in 45 of 8594 chromosomes (freq. 0.005236), European (Non-Finnish) in 2 of 54166 chromosomes (freq. 0.00003692), Latino in 3 of 9428 chromosomes (freq. 0.0003182), but was not seen in East Asian, European (Finnish), South Asian and Other populations, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin; the ClinVar database (classified as a benign variant by GeneDx, Invitae and likely benign by Ambry Genetics, Emory Genetics Laboratory), GeneInsight COGR (2x, classified benign and as uncertain significance) and BRCA Share UMD (38x as likely neutral). In UMD the variant was identified with co-occurring pathogenic BRCA1 and BRCA2 variants (BRCA1 c.342_343delTC p.Pro115X, c.1423_1508del p.Ser475AlafsX2 and BRCA2 c.6984delG p.Glu2328AspfsX39, c.4889C>G, p.Ser1630X) increasing the likelihood that the p.Gly1371Gly variant does not have clinical significance. The p.Gly1371Gly variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The p.Gly1371Gly variant occurs outside of the splicing consensus sequence and 2 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Hereditary Cancer Genetics group,Vall d'Hebron Institute of Oncology RCV000198974 SCV000916349 benign Hereditary breast and ovarian cancer syndrome 2019-03-01 no assertion criteria provided research

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