rs200662943
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000384.3(APOB):c.574G>A(p.Val192Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,614,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.574G>A | p.Val192Ile | missense_variant | Exon 6 of 29 | 1 | NM_000384.3 | ENSP00000233242.1 | ||
APOB | ENST00000399256.4 | c.574G>A | p.Val192Ile | missense_variant | Exon 6 of 17 | 1 | ENSP00000382200.4 | |||
APOB | ENST00000673739.2 | n.420G>A | non_coding_transcript_exon_variant | Exon 5 of 25 | ENSP00000501110.2 | |||||
APOB | ENST00000673882.2 | n.420G>A | non_coding_transcript_exon_variant | Exon 5 of 23 | ENSP00000501253.2 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251400Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135874
GnomAD4 exome AF: 0.000127 AC: 186AN: 1461862Hom.: 1 Cov.: 32 AF XY: 0.000121 AC XY: 88AN XY: 727232
GnomAD4 genome AF: 0.000125 AC: 19AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74398
ClinVar
Submissions by phenotype
not provided Uncertain:3
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Identified in patients with combined hyperlipidemia and/or high LDL-C in the published literature (Gill et al., 2021; Rimbert et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as p.(V165I); This variant is associated with the following publications: (PMID: 33303402, 35047021) -
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Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Uncertain:1Benign:1
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Hypercholesterolemia, familial, 1 Uncertain:1
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Cardiovascular phenotype Benign:1
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