rs775839180
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_014339.7(IL17RA):c.812G>A(p.Arg271His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R271Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_014339.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL17RA | NM_014339.7 | c.812G>A | p.Arg271His | missense_variant | 8/13 | ENST00000319363.11 | |
IL17RA | NM_001289905.2 | c.812G>A | p.Arg271His | missense_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL17RA | ENST00000319363.11 | c.812G>A | p.Arg271His | missense_variant | 8/13 | 1 | NM_014339.7 | P2 | |
IL17RA | ENST00000612619.2 | c.812G>A | p.Arg271His | missense_variant | 8/12 | 5 | A2 | ||
IL17RA | ENST00000694951.1 | n.770G>A | non_coding_transcript_exon_variant | 6/7 | |||||
IL17RA | ENST00000694950.1 | c.*317G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152122Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000560 AC: 14AN: 250164Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135326
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461384Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38AN XY: 726962
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152122Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74322
ClinVar
Submissions by phenotype
Immunodeficiency 51 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 05, 2022 | This variant is present in population databases (rs775839180, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 271 of the IL17RA protein (p.Arg271His). This variant has not been reported in the literature in individuals affected with IL17RA-related conditions. ClinVar contains an entry for this variant (Variation ID: 340580). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 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