chr2-21005148-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000384.3(APOB):āc.11720A>Gā(p.Asp3907Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000768 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.11720A>G | p.Asp3907Gly | missense_variant | 26/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.11720A>G | p.Asp3907Gly | missense_variant | 26/29 | 1 | NM_000384.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251306Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135808
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461742Hom.: 0 Cov.: 34 AF XY: 0.0000468 AC XY: 34AN XY: 727176
GnomAD4 genome AF: 0.000322 AC: 49AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2023 | Identified in at least one individual in the Insulin Resistance Atherosclerosis Family Study (IRASFS) cohort, which investigated linkage between complex cardiometabolic phenotypes and various loci (Hellwege et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24719370) - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at