rs149357946
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000384.3(APOB):c.3052G>A(p.Ala1018Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.3052G>A | p.Ala1018Thr | missense_variant | 20/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.3052G>A | p.Ala1018Thr | missense_variant | 20/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000673739.2 | c.*2358G>A | 3_prime_UTR_variant, NMD_transcript_variant | 19/25 | |||||
APOB | ENST00000673882.2 | c.*2358G>A | 3_prime_UTR_variant, NMD_transcript_variant | 19/23 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251394Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135860
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727226
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Apr 08, 2022 | The c.3052G>A (p.Ala1018Thr) missense variant identified in the APOB gene has not been reported in affected individuals in the literature. The variant has four heterozygous in the gnomAD(v3) and eleven heterozygous in TOPMed Freeze 8 database suggesting it is not a common benign variant in the populations represented in that database. The variant affects a moderately conserved residue and multiple in silico prediction tools provide conflicting predictions about the potential pathogenicity of this variant (CADD=22.1, REVEL score = 0.180). Based on the available evidence, the c.3052G>A (p.Ala1018Thr) variant identified in the APOB gene is reported as a Variant of Uncertain Significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2023 | The p.A1018T variant (also known as c.3052G>A), located in coding exon 20 of the APOB gene, results from a G to A substitution at nucleotide position 3052. The alanine at codon 1018 is replaced by threonine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs149357946. Based on data from ExAC, the A allele has an overall frequency of less than 0.01% (2/106206). Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.56% (1/178) Japanese alleles. This amino acid position is not well 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 variant remains unclear. - |
Hypercholesterolemia, familial, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Robarts Research Institute, Western University | Jan 02, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at