rs1058861
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000628.5(IL10RB):c.727G>A(p.Ala243Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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. A243S) has been classified as Likely benign.
Frequency
Consequence
NM_000628.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL10RB | NM_000628.5 | c.727G>A | p.Ala243Thr | missense_variant | 6/7 | ENST00000290200.7 | |
IFNAR2-IL10RB | NM_001414505.1 | c.1387G>A | p.Ala463Thr | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL10RB | ENST00000290200.7 | c.727G>A | p.Ala243Thr | missense_variant | 6/7 | 1 | NM_000628.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152104Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251490Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135918
GnomAD4 exome AF: 0.000150 AC: 219AN: 1461752Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 98AN XY: 727196
GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152104Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74288
ClinVar
Submissions by phenotype
Inflammatory bowel disease 25 Uncertain:2
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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 243 of the IL10RB protein (p.Ala243Thr). This variant is present in population databases (rs1058861, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IL10RB-related conditions. ClinVar contains an entry for this variant (Variation ID: 339695). 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 IL10RB 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 14, 2022 | BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at