rs780537483
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_000384.3(APOB):c.2675C>T(p.Pro892Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,036 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P892P) has been classified as Likely benign.
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.2675C>T | p.Pro892Leu | missense_variant | 18/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.2675C>T | p.Pro892Leu | missense_variant | 18/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000673739.2 | c.*1981C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/25 | |||||
APOB | ENST00000673882.2 | c.*1981C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/23 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251400Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135872
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727244
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74328
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 10, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 29, 2022 | The p.P892L variant (also known as c.2675C>T), located in coding exon 18 of the APOB gene, results from a C to T substitution at nucleotide position 2675. The proline at codon 892 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at