Overview

Clinical Phenotype: Hyperlipoproteinemia Type IIa
Position: (GRCh38/hg38):Chr19:44908906 G>T
Position: (GRCh37/hg19):Chr19:45412163 G>T
Transcript: NM_000041; ENSG00000130203
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Nonsense
Codon Change: GAA to TAA
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4

Findings

This variant was identified in a Chilean child who was homozygous for the mutation and suffered from presumed familial hypercholesterolemia, also known as hyperlipoproteinemia type IIa (Sánchez et al., 2021). He had high levels of total cholesterol and low-density lipoprotein (LDL) cholesterol in blood.

The variant was absent from the gnomAD variant database (v2.1.1, Apr 2022).

Biological Effect

The biological effect of this variant is unknown, but it is predicted to result in either a truncated protein, lacking part of the hinge region and the entire C-terminal domain, or in loss of expression due to activation of the nonsense-mediated mRNA decay pathway. Its PHRED-scaled CADD score, which integrates diverse information in silico, was 37, suggesting a deleterious effect (CADD v.1.6, Apr 2022).

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References

Paper Citations

1. Sánchez A, Bustos P, Honorato P, Sáez K, Elim-Jannes C, Barriga N, Ibieta G, Pérez L, Alonso R, Radojkovic C, Asenjo S. [Identification of genetic variants associated with familial hypercholesterolemia in Chilean children and adolescents]. Rev Med Chil. 2021 Sep;149(9):1267-1274. PubMed.

Further Reading

No Available Further Reading