5-87376401-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_002890.3(RASA1):c.2020C>T(p.Arg674Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R674H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002890.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASA1 | NM_002890.3 | c.2020C>T | p.Arg674Cys | missense_variant | 16/25 | ENST00000274376.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASA1 | ENST00000274376.11 | c.2020C>T | p.Arg674Cys | missense_variant | 16/25 | 1 | NM_002890.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250552Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135408
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461566Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727074
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74288
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Capillary malformation-arteriovenous malformation syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 674 of the RASA1 protein (p.Arg674Cys). This variant is present in population databases (rs370631681, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RASA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 575599). 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 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. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at