chr2-21013287-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000384.3(APOB):c.4089C>A(p.Tyr1363*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000384.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.4089C>A | p.Tyr1363* | stop_gained | 25/29 | 1 | NM_000384.3 | ENSP00000233242.1 | ||
APOB | ENST00000673739.2 | n.*3395C>A | non_coding_transcript_exon_variant | 24/25 | ENSP00000501110.2 | |||||
APOB | ENST00000673739.2 | n.*3395C>A | 3_prime_UTR_variant | 24/25 | ENSP00000501110.2 | |||||
APOB | ENST00000673882.2 | n.*3184C>A | downstream_gene_variant | ENSP00000501253.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2025 | This sequence change creates a premature translational stop signal (p.Tyr1363*) in the APOB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypocholesterolemia (PMID: 17043676). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 477784). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at