2-21012072-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000384.3(APOB):c.4796G>A(p.Arg1599His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,030 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. R1599C) has been classified as Likely benign.
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.4796G>A | p.Arg1599His | missense_variant | Exon 26 of 29 | 1 | NM_000384.3 | ENSP00000233242.1 | ||
APOB | ENST00000673739.2 | n.*4102G>A | non_coding_transcript_exon_variant | Exon 25 of 25 | ENSP00000501110.2 | |||||
APOB | ENST00000673739.2 | n.*4102G>A | 3_prime_UTR_variant | Exon 25 of 25 | ENSP00000501110.2 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000140 AC: 35AN: 250354Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135258
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461820Hom.: 0 Cov.: 35 AF XY: 0.0000440 AC XY: 32AN XY: 727202
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
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Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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