Overview

Clinical Phenotype: Blood Lipids/Lipoproteins, Hyperlipoproteinemia Type IIb
Position: (GRCh38/hg38):Chr19:44907785 G>A
Position: (GRCh37/hg19):Chr19:45411042 G>A
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs111833428
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Silent
Codon Change: GCG to GCA
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 3

Findings

This silent substitution was found to be associated with plasma triglycerides in an analysis of 623 non-Hispanic Whites, after adjusting for the presence of the common APOE alleles APOE2 and APOE4 (Radwan et al., 2014). The association was absent from 788 African Blacks.

The variant was also reported in a French patient in a cohort of nearly 6,000 unrelated individuals with primary dyslipidemia (Abou Khalil et al., 2022). The carrier had elevated triglycerides in blood and was diagnosed with familial combined hyperlipidemia, also known as hyperlipoproteinemia type IIb. Their APOE genotype was APOE3/E3.

This variant was found at a frequency of 0.00021 in the gnomAD variant database, including 58 heterozygotes, most of European ancestry (v2.1.1, Apr2022).

Biological Effect

The biological effect of this variant is unknown, but its PHRED-scaled CADD score, which integrates diverse information in silico, did not reach 20, a commonly used threshold to predict deleteriousness (CADD v.1.6, Apr 2022).

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References

Paper Citations

1. Radwan ZH, Wang X, Waqar F, Pirim D, Niemsiri V, Hokanson JE, Hamman RF, Bunker CH, Barmada MM, Demirci FY, Kamboh MI. Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. whites and African blacks. PLoS One. 2014;9(12):e114618. Epub 2014 Dec 12 PubMed.
2. Abou Khalil Y, Marmontel O, Ferrières J, Paillard F, Yelnik C, Carreau V, Charrière S, Bruckert E, Gallo A, Giral P, Philippi A, Bluteau O, Boileau C, Abifadel M, Di-Filippo M, Carrié A, Rabès JP, Varret M. APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. Int J Mol Sci. 2022 May 21;23(10) PubMed.

Further Reading

No Available Further Reading