Overview

Clinical Phenotype: Hyperlipoproteinemia Type III
Position: (GRCh38/hg38):Chr19:44908657 C>T
Position: (GRCh37/hg19):Chr19:45411914 C>T
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs11542037
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CGG to TGG
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4

Findings

This variant was identified in a 49-year-old Spanish individual from the Aragon Workers Health Study, a longitudinal cohort study of cardiovascular risk factors and subclinical atherosclerosis in workers of a Spanish factory (Bea et al., 2023). The variant was identified by targeted sequencing of APOE exon 4. The carrier was diagnosed with hyperlipoproteinemia type III (HLPP3), also known as dysbetalipoproteinemia, a condition characterized by the accumulation of remnants of triglyceride-rich lipoproteins. In this study, two ratios were used for diagnosis: non-HDLc/ApoB >=1.7 and triglycerides/ApoB >=1.35. Although HLPP3 is often associated with atherosclerotic cardiovascular disease, this disease was not diagnosed at the time of the study. The carrier was an APOE3 homozygote.

A single heterozygote carrier of Latino/Admixed American ancestry was reported in the gnomAD variant database (gnomAD v2.1.1, Jun 2023).

Biological Effect

The biological effect of this variant is unknown, but at least three of four in silico algorithms predicted it is deleterious (Bea et al., 2023). Moreover, its PHRED-scaled CADD score (26.1), which integrates diverse information in silico, was above 20, a commonly used threshold to predict deleteriousness (CADD v.1.6, Jun 2023).

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References

Paper Citations

1. Bea AM, Larrea-Sebal A, Marco-Benedi V, Uribe KB, Galicia-Garcia U, Lamiquiz-Moneo I, Laclaustra M, Moreno-Franco B, Fernandez-Corredoira P, Olmos S, Civeira F, Martin C, Cenarro A. Contribution of APOE Genetic Variants to Dyslipidemia. Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):1066-1077. Epub 2023 Apr 13 PubMed.

Further Reading

No Available Further Reading