2-21015388-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate
The NM_000384.3(APOB):c.3490A>G(p.Arg1164Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1164K) has been classified as Likely benign.
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.3490A>G | p.Arg1164Gly | missense_variant | 22/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.3490A>G | p.Arg1164Gly | missense_variant | 22/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000673739.2 | c.*2796A>G | 3_prime_UTR_variant, NMD_transcript_variant | 21/25 | |||||
APOB | ENST00000673882.2 | c.*2585A>G | 3_prime_UTR_variant, NMD_transcript_variant | 20/23 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251436Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135886
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 727248
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74474
ClinVar
Submissions by phenotype
Familial hypobetalipoproteinemia 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | case-control | Metabolic Liver Diseases Lab, Fondazione IRCCS Ca Granda Policlinico, University of Milan | Dec 01, 2018 | - - |
Hypercholesterolemia, familial, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Laboratory of Genetics and Molecular Cardiology, University of São Paulo | Mar 01, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in a cohort of individuals with nonalcoholic fatty liver disease/hepatocellular carcinoma and detailed clinical information was not provided (Pelusi et al., 2019); Also known as R1137G; This variant is associated with the following publications: (PMID: 30842500) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2021 | The p.R1164G variant (also known as c.3490A>G), located in coding exon 22 of the APOB gene, results from an A to G substitution at nucleotide position 3490. The arginine at codon 1164 is replaced by glycine, an amino acid with dissimilar properties. Another alteration affecting the same amino acid, p.R1164T (c.3491G>C), has been reported in association with familial hypercholesterolemia (FH) (Alves AC et al. Hum. Mol. Genet., 2014 Apr;23:1817-28). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at