ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.114G>A (p.Lys38=) (rs1800062)

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Total submissions: 20
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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) RCV000111799 SCV000244845 benign Breast-ovarian cancer, familial 1 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.05769 (Asian), derived from 1000 genomes (2012-04-30).
Invitae RCV000047360 SCV000075373 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000111799 SCV000154026 benign Breast-ovarian cancer, familial 1 2014-03-13 criteria provided, single submitter literature only
Ambry Genetics RCV000162531 SCV000212930 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 RCV000111799 SCV000403076 benign Breast-ovarian cancer, familial 1 2018-03-06 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000047360 SCV000494301 benign Hereditary breast and ovarian cancer syndrome 2014-02-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV000474769 SCV000540973 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000496808 SCV000586864 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001281737 SCV000602711 benign none provided 2020-09-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162531 SCV000682939 benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
GeneKor MSA RCV000496808 SCV000693597 benign not specified 2017-11-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000496808 SCV000806892 benign not specified 2017-06-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000496808 SCV001470156 benign not specified 2020-06-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111799 SCV000144344 benign Breast-ovarian cancer, familial 1 2006-07-19 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000111799 SCV000189325 benign Breast-ovarian cancer, familial 1 2011-03-03 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496808 SCV000591239 benign not specified no assertion criteria provided clinical testing The BRCA1 p.Lys38= variant was identified in 16 of 604 proband chromosomes (frequency: 0.026) from Asian and Colombian individuals or families with hereditary breast and/or ovarian cancer or early-onset breast cancer and was present in 3 of 142 control chromosomes (frequency: 0.021) from healthy individuals (Torres_2007_17080309, Ho_2000_10951344, Chen_2003_12602912, Song_2006_16835750, Toh_2008_18431501). The variant was also identified in dbSNP (ID: rs1800062) as “With Uncertain significance, other allele”, ClinVar and Clinvitae (11x classified as benign by ENIGMA, Laboratory Corporation of America, Baylor Miraca Genetics, British Columbia Cancer Agency (COGR), Sinai Health System (COGR), ARUP Laboratories, Invitae, Counsyl, Ambry Genetics, SCRP, BIC; 2x classified as likely benign by Illumina Clinical Services and CHEO), GeneInsight-COGR (classified as likely benign/benign by COGR consensus and Sinai Health System), LOVD 3.0 (11 entries, classified as does not affect function or not classified), UMD-LSDB (37 entries, 2 of which have co-occurring pathogenic variants), BIC Database (18 entries, classified as not pathogenic), and the Zhejiang Colon Cancer Database (5 entries classified as no known pathogenicity). The variant was not identified in the COSMIC, MutDB, or ARUP Laboratories databases. The variant was identified in control databases in 1135 of 276592 chromosomes (18 homozygous) at a frequency of 0.004 increasing the likelihood this could be a low frequency variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 4 of 23984 chromosomes (freq: 0.0002), Other in 13 of 6450 chromosomes (freq: 0.002), Latino in 368 of 34346 chromosomes (freq: 0.01), European Non-Finnish in 2 of 126380 chromosomes (freq: 0.00002), East Asian in 741 of 18846 chromosomes (freq: 0.04), European Finnish in 1 of 25776 chromosomes (freq: 0.00004), and South Asian in 6 of 30688 chromosomes (freq: 0.0002) while the variant was not observed in the Ashkenazi Jewish population. The p.Lys38= 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 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. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000111799 SCV000733682 benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000656647 SCV000778780 benign not provided 2016-12-19 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162531 SCV000787892 likely benign Hereditary cancer-predisposing syndrome 2017-09-13 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000111799 SCV001241896 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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