ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5406+8T>C (rs55946644)

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Total submissions: 19
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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) RCV000112640 SCV000244535 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 0.02033 (African), derived from 1000 genomes (2012-04-30).
Counsyl RCV000112640 SCV000220276 benign Breast-ovarian cancer, familial 1 2014-04-28 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000168523 SCV000227831 benign not specified 2014-07-02 criteria provided, single submitter clinical testing
Invitae RCV000204121 SCV000262328 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Vantari Genetics RCV000210819 SCV000267001 benign Hereditary cancer-predisposing syndrome 2016-02-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000112640 SCV000403054 likely benign Breast-ovarian cancer, familial 1 2018-07-23 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 RCV000204121 SCV000494360 benign Hereditary breast and ovarian cancer syndrome 2014-04-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV000458390 SCV000540968 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000112640 SCV000575718 likely benign Breast-ovarian cancer, familial 1 2015-08-07 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000168523 SCV000586911 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000210819 SCV000683310 benign Hereditary cancer-predisposing syndrome 2015-06-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112640 SCV000744583 benign Breast-ovarian cancer, familial 1 2017-05-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000168523 SCV000806972 benign not specified 2016-10-03 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170588 SCV001333176 benign Breast and/or ovarian cancer 2017-11-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286036 SCV001472554 benign none provided 2020-08-25 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112640 SCV000145495 benign Breast-ovarian cancer, familial 1 2006-07-19 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353492 SCV000591625 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 c.5406+8T>C variant was identified in the literature however the frequency of this variant in an affected population was not provided. The variant was also identified in dbSBP (ID: rs55946644) as other, ClinVar (8x benign: ENIGMA, Invitae, Vantari Genetics, LabCorp, Baylor Miraca Genetics, Counsyl, Emory Genetics, BIC; 2x likely benign: Illumina, CHEO), Genesight-COGR (classified as benign by a clinical laboratory), LOVD 3.0 (7 entries, 2x predicted neutral, 1x no splicing defect), BIC Database (16x not pathogenic/low clinical significance, MAF>0.01) databases. The variant was not identified in the COSMIC, MutDB, UMD-LSDB, ARUP Laboratories, or Zhejiang University databases. The variant was also identified by our laboratory in 2 individuals with breast cancer. The variant was identified in control databases in 400 of 277096 chromosomes at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 351 of 24014 chromosomes (freq: 0.015). Functional studies using splicing reporter minigene assays and patient RNA analysis indicate no effect on splicing (Steffensen 2014, Bonnet 2008, Thery 2011, Houdayer 2012). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
True Health Diagnostics RCV000210819 SCV000787911 likely benign Hereditary cancer-predisposing syndrome 2017-12-08 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000112640 SCV001238703 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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