ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5468-10C>A (rs8176316)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 18
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112663 SCV000244520 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 0.01626 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000167846 SCV000077020 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000112663 SCV000153994 benign Breast-ovarian cancer, familial 1 2014-01-02 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000168524 SCV000228063 benign not specified 2015-07-08 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000112663 SCV000267721 benign Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167846 SCV000494331 benign Hereditary breast and ovarian cancer syndrome 2014-04-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000463892 SCV000540966 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282693 SCV000602676 benign none provided 2020-08-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000580840 SCV000683320 benign Hereditary cancer-predisposing syndrome 2014-12-06 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000168524 SCV000806974 benign not specified 2017-07-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000168524 SCV001469398 benign not specified 2020-06-14 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112663 SCV000145527 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000112663 SCV000189894 likely benign Breast-ovarian cancer, familial 1 2014-07-24 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353821 SCV000591634 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 c.5468-10C>A variant was identified in 3 of 4550 proband chromosomes from individuals or families with breast or ovarian cancer (frequency: 0.001); however control chromosomes were not included in these studies (Borg 2010, Tommasi 2008, Uhrhammer 2008).The variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. One functional study did not find any effect of the variant on splicing (Houdayer 2012), and in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts a greater than 10% difference in splicing in only 2 of 5 different programs, though this information is not predictive enough to rule out pathogenicity. The variant was also identified in HGMD, LOVD, and the BIC database (15X with unknown clinical importance), and UMD (31X as a neutral variant). In UMD the variant was identified in four samples as co-occurring a pathogenic variant (two in BRCA1 and two in BRCA2), increasing the likelihood that the variant does not have clinical importance. The variant was listed in dbSNP (ID: rs8176316) with a minor allele frequency of 0.004 (1000 Genomes Project) and an average heterozygosity of 0.007+/-0.060. Furthermore, this variant occurs at a frequency of greater than 1% in some populations of origin and is therefore classified as a polymorphism (African American alleles in the NHLBI Exome Sequencing Project (Exome Variant Server) (frequency: 0.014), HapMap-YRI (frequency: 0.018), HAPMAP-LWK (frequency: 0.017), and HAPMAP-ASW (frequency: 0.01)). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Brotman Baty Institute,University of Washington RCV000112663 SCV001237527 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000168524 SCV001906339 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000168524 SCV001932453 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000168524 SCV001958801 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.