Overview

Clinical Phenotype: Hyperlipoproteinemia Type IIb
Position: (GRCh38/hg38):Chr19:44909041 G>A
Position: (GRCh37/hg19):Chr19:45412298 G>A
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs762906934
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GAG to AAG
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4

Findings

This variant was identified in a French patient from a cohort of nearly 6,000 unrelated individuals with primary dyslipidemia (Abou Khalil et al., 2022). The carrier had elevated triglycerides in blood and cardiovascular disease. They were diagnosed with familial combined hyperlipidemia, also known as hyperlipoproteinemia type IIb. The carrier had a family history of dyslipidemia and their APOE genotype was APOE3/E3.

The variant was found in the gnomAD variant database at a frequency of 0.000007, including a single heterozygote of African ancestry (gnomAD v3.1.1, Nov 2021).

Biological Effect

The biological effect of this variant is unknown. Multiple computational algorithms, including SIFT, PolyPhen2, Muation Taster, and Provean predicted it is benign. Its PHRED-scaled CADD score, which integrates diverse information in silico, was 19.7, predicted to be among the top 10 percent of the most deleterious substitutions in the human genome (Abou Khalil et al., 2022). Note that some classifications use 20 as a threshold score (corresponding to the top 1 percent) for predicting a damaging effect.

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References

Paper Citations

1. 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