rs145862664
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The ENST00000233242.5(APOB):āc.1648G>Cā(p.Asp550His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,613,450 control chromosomes in the GnomAD database, including 12 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
ENST00000233242.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.1648G>C | p.Asp550His | missense_variant | 13/29 | ENST00000233242.5 | NP_000375.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.1648G>C | p.Asp550His | missense_variant | 13/29 | 1 | NM_000384.3 | ENSP00000233242 | P1 | |
APOB | ENST00000399256.4 | c.1648G>C | p.Asp550His | missense_variant | 13/17 | 1 | ENSP00000382200 | |||
APOB | ENST00000673739.2 | c.*954G>C | 3_prime_UTR_variant, NMD_transcript_variant | 12/25 | ENSP00000501110 | |||||
APOB | ENST00000673882.2 | c.*954G>C | 3_prime_UTR_variant, NMD_transcript_variant | 12/23 | ENSP00000501253 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000159 AC: 40AN: 250878Hom.: 1 AF XY: 0.000133 AC XY: 18AN XY: 135652
GnomAD4 exome AF: 0.000462 AC: 675AN: 1461130Hom.: 12 Cov.: 32 AF XY: 0.000431 AC XY: 313AN XY: 726894
GnomAD4 genome AF: 0.000204 AC: 31AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74484
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Familial hypobetalipoproteinemia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 05, 2023 | - - |
Hypercholesterolemia Benign:1
Likely benign, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Aug 01, 2016 | Found in patient having exome sequencing for an unrelated indication. No known history hypercholesterolemia. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a likely benign variant (ClinVar Variant ID# 375860; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at