8-107251871-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001146.5(ANGPT1):c.1481G>A(p.Arg494Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,613,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R494P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001146.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANGPT1 | NM_001146.5 | c.1481G>A | p.Arg494Gln | missense_variant | 9/9 | ENST00000517746.6 | |
ANGPT1 | NM_001199859.3 | c.1478G>A | p.Arg493Gln | missense_variant | 9/9 | ||
ANGPT1 | NM_001314051.2 | c.881G>A | p.Arg294Gln | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANGPT1 | ENST00000517746.6 | c.1481G>A | p.Arg494Gln | missense_variant | 9/9 | 1 | NM_001146.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152098Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250950Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135614
GnomAD4 exome AF: 0.0000753 AC: 110AN: 1461536Hom.: 0 Cov.: 30 AF XY: 0.0000853 AC XY: 62AN XY: 727050
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152216Hom.: 1 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74420
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 494 of the ANGPT1 protein (p.Arg494Gln). This variant is present in population databases (rs377442517, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with angioedema (PMID: 28601681). ClinVar contains an entry for this variant (Variation ID: 1506084). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect ANGPT1 function (PMID: 28601681). 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