rs1060499842
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PVS1PM2BP6_Moderate
The NM_000384.3(APOB):c.26_33del(p.Leu9ProfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000238 in 1,257,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000024 ( 0 hom. )
Consequence
APOB
NM_000384.3 frameshift
NM_000384.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.34
Genes affected
APOB (HGNC:603): (apolipoprotein B) This gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels. [provided by RefSeq, Dec 2019]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 209 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 2-21043912-GCAGCGCCA-G is Benign according to our data. Variant chr2-21043912-GCAGCGCCA-G is described in ClinVar as [Benign]. Clinvar id is 402371.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.26_33del | p.Leu9ProfsTer46 | frameshift_variant | 1/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.26_33del | p.Leu9ProfsTer46 | frameshift_variant | 1/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000399256.4 | c.26_33del | p.Leu9ProfsTer46 | frameshift_variant | 1/17 | 1 | |||
APOB | ENST00000673739.2 | c.26_33del | p.Leu9ProfsTer46 | frameshift_variant, NMD_transcript_variant | 1/25 | ||||
APOB | ENST00000673882.2 | c.26_33del | p.Leu9ProfsTer46 | frameshift_variant, NMD_transcript_variant | 1/23 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000238 AC: 3AN: 1257884Hom.: 0 AF XY: 0.00000162 AC XY: 1AN XY: 618358
GnomAD4 exome
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3
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618358
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Likely rs17240441, a single common 9 bp deletion - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at