ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3418A>G (p.Ser1140Gly) (rs2227945)

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Total submissions: 22
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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) RCV000112092 SCV000244340 benign Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000592. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.04878 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000048187 SCV000076200 benign Hereditary breast and ovarian cancer syndrome 2020-11-23 criteria provided, single submitter clinical testing
Counsyl RCV000112092 SCV000153996 likely benign Breast-ovarian cancer, familial 1 2014-01-02 criteria provided, single submitter literature only
Michigan Medical Genetics Laboratories,University of Michigan RCV000112092 SCV000195920 benign Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120277 SCV000202267 benign not specified 2014-03-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162594 SCV000213012 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as 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.
Illumina Clinical Services Laboratory,Illumina RCV000112092 SCV000403060 likely benign Breast-ovarian cancer, familial 1 2018-02-22 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000048187 SCV000494372 benign Hereditary breast and ovarian cancer syndrome 2013-10-15 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000112092 SCV000575714 likely benign Breast-ovarian cancer, familial 1 2015-12-11 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000048187 SCV000576441 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283690 SCV000602707 benign none provided 2020-09-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162594 SCV000683103 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112092 SCV000744635 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120277 SCV000806933 benign not specified 2017-05-05 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197692 SCV001368471 benign Familial cancer of breast 2018-09-25 criteria provided, single submitter clinical testing This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034741 SCV000043167 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000120277 SCV000084429 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000112092 SCV000144758 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Department of Medical Genetics, University Hospital of North Norway RCV000112092 SCV000301433 benign Breast-ovarian cancer, familial 1 2016-05-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120277 SCV000591444 benign not specified no assertion criteria provided clinical testing The BRCA1, c.3418A>G, p.Ser1140Gly variant has been reported in the literature in at least 18/44788 proband chromosomes of individuals with sporadic as well as high-risk breast and /or ovarian cancer. It has also been found in 4/5118 control chromosomes evaluated (Tavtigian_2006_16014699, Abkevich_2004_15235020, Johnson_2007_17341484, McKean-Cowdin_2005_15726418, Alsop_2012_22711857, Elstrodt_2006_16397213, Tazzite_2012_22425665, Velasco_2005_15937982, Soegaard_2008_18559594). It is listed in the dbSNP database (ID#: rs2227945) as coming from a clinical source with a minor allele frequency of 0.011, having been observed in 25 chromosomes (1000 genomes), increasing the likelihood that this is benign variant. It has been listed in the UMD (x14 as neutral), BIC (x29 as UV) and the CNPHI (ACMG 3) databases. In addition, in the UMD mutation database, the variant was observed to co-occur with pathogenic BRCA1 [c.2890G>T (p.Gly964X) and c.415C>T (p.Gln139X)] as well as BRCA2 [c.2092delC (p.Leu698TyrfsX32)] variants, increasing the likelihood that p.Ser1140Gly is benign. This residue is not conserved in mammals and the variant amino acid Glycine (Gly) is present in the mouse. Computational analyses (PolyPhen, SIFT, AlignGVGD) does not predict any effect on the protein function, increasing the likelihood this variant does not have functional significance. In summary, based on the above information, this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000034741 SCV000778747 benign not provided 2017-10-09 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162594 SCV000787902 benign Hereditary cancer-predisposing syndrome 2018-01-03 no assertion criteria provided clinical testing

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