ClinVar Miner

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

gnomAD frequency: 0.00701  dbSNP: rs769455
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Total submissions: 9
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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: seen in unaffected individuals, 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 disorder 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.

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