Overview

Clinical Phenotype: Hyperlipoproteinemia Type IIb
Position: (GRCh38/hg38):Chr19:44906655 A>G
Position: (GRCh37/hg19):Chr19:45409912 A>G
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs144354013
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: ACA to GCA
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 2

Findings

This variant, located in the sequence coding for the signal peptide of the ApoE protein, was identified 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/E4.

The variant was present in the gnomAD variant database at a frequency of 0.00009, including 13 heterozygotes, 11 of whom were of Latino/Admixed American ancestry (gnomAD v3.1.1, Nov 2021).

Biological Effect

The biological effect of this variant is unknown, but multiple computational algorithms predicted it is benign (Abou Khalil et al., 2022). In particular, its PHRED-scaled CADD score (0.29), which integrates diverse information in silico, was well below 20, a commonly used threshold to predict deleteriousness. Additional in silico data were reported in a study that applied 16 predictive algorithms based on sequence homology, supervised-learning, protein-sequence and structure, and consensus sequence identification (Pires et al., 2017 see supplementary table 2).

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

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.
2. Pires AS, Porto WF, Franco OL, Alencar SA. In silico analyses of deleterious missense SNPs of human apolipoprotein E3. Sci Rep. 2017 May 30;7(1):2509. PubMed.

Further Reading

No Available Further Reading