chr11-116835851-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000039.3(APOA1):āc.761T>Gā(p.Leu254Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,794 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L254L) has been classified as Likely benign.
Frequency
Consequence
NM_000039.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOA1 | NM_000039.3 | c.761T>G | p.Leu254Arg | missense_variant | 4/4 | ENST00000236850.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOA1 | ENST00000236850.5 | c.761T>G | p.Leu254Arg | missense_variant | 4/4 | 1 | NM_000039.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249214Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135482
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460794Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726714
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 17, 2023 | 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. 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 APOA1 protein function. This variant has not been reported in the literature in individuals affected with APOA1-related conditions. This variant is present in population databases (rs775381241, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 254 of the APOA1 protein (p.Leu254Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at