ClinVar Miner

Submissions for variant NM_000041.4(APOE):c.487C>T (p.Arg163Cys)

gnomAD frequency: 0.00701  dbSNP: rs769455
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000884152 SCV001027508 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000884152 SCV001836588 benign not provided 2019-07-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24239320, 26377243, 3243553, 22069485, 20981092, 11500500, 24507774)
H3Africa Consortium RCV001777143 SCV002014648 benign not specified 2020-10-28 criteria provided, single submitter research While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.069, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error.
Genetic Services Laboratory, University of Chicago RCV001777143 SCV002065969 benign not specified 2021-02-15 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV000884152 SCV002503532 uncertain significance not provided 2020-11-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002326680 SCV002633850 benign Cardiovascular phenotype 2019-09-06 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.
PreventionGenetics, part of Exact Sciences RCV003924846 SCV004742648 likely benign APOE-related condition 2023-08-05 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
OMIM RCV000019432 SCV000039721 pathogenic Familial type 3 hyperlipoproteinemia 1988-11-01 no assertion criteria provided literature only
Reproductive Health Research and Development, BGI Genomics RCV000019432 SCV001142489 likely pathogenic Familial type 3 hyperlipoproteinemia 2020-01-06 no assertion criteria provided curation NM_000041.2:c.487C>T in the APOE gene has an allele frequency of 0.021 in African subpopulation in the gnomAD database. The p.Arg163Cys (NM_000041.2:c.487C>T) variant has been reported to be associated with type III hyperlipoproteinemia (PMID: 25502880; 26802169). In vitro functional studies suggest that the p.Arg163Cys variant may affect protein function (PMID: 26802169). Pathogenic computational verdict because pathogenic predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, MVP, MutationAssessor, MutationTaster, REVEL and SIFT. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PS3; PP4; PP3.

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.