11-116821139-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000482.4(APOA4):c.919G>C(p.Val307Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_000482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOA4 | NM_000482.4 | c.919G>C | p.Val307Leu | missense_variant | 3/3 | ENST00000357780.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOA4 | ENST00000357780.5 | c.919G>C | p.Val307Leu | missense_variant | 3/3 | 1 | NM_000482.4 | P1 | |
ENST00000645414.1 | n.288C>G | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250606Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135670
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461376Hom.: 0 Cov.: 86 AF XY: 0.0000193 AC XY: 14AN XY: 727010
GnomAD4 genome ? AF: 0.000250 AC: 38AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 307 of the APOA4 protein (p.Val307Leu). This variant is present in population databases (rs5108, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with APOA4-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APOA4 protein function with a negative predictive value of 80%. 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