rs777497625
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000384.3(APOB):c.7209G>T(p.Lys2403Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.7209G>T | p.Lys2403Asn | missense_variant | 26/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.7209G>T | p.Lys2403Asn | missense_variant | 26/29 | 1 | NM_000384.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249622Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134980
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461066Hom.: 0 Cov.: 61 AF XY: 0.00000275 AC XY: 2AN XY: 726774
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces lysine with asparagine at codon 2403 of the APOB protein (p.Lys2403Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs777497625, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with APOB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at