rs121909601
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000628.5(IL10RB):c.477G>A(p.Trp159Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
IL10RB
NM_000628.5 stop_gained
NM_000628.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.65
Genes affected
IL10RB (HGNC:5965): (interleukin 10 receptor subunit beta) The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 21-33279897-G-A is Pathogenic according to our data. Variant chr21-33279897-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 16924.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL10RB | NM_000628.5 | c.477G>A | p.Trp159Ter | stop_gained | 4/7 | ENST00000290200.7 | |
IFNAR2-IL10RB | NM_001414505.1 | c.1137G>A | p.Trp379Ter | stop_gained | 10/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL10RB | ENST00000290200.7 | c.477G>A | p.Trp159Ter | stop_gained | 4/7 | 1 | NM_000628.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inflammatory bowel disease 25 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 19, 2009 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2019 | This sequence change creates a premature translational stop signal (p.Trp159*) in the IL10RB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with IL10RB-related disease in one family (PMID: 19890111) and has been observed in additional individuals with IL10RB-related disease (PMID: 25373860, 27699073). ClinVar contains an entry for this variant (Variation ID: 16924). This variant has been reported to affect IL10RB protein function in patient derived cells (PMID: 19890111). Loss-of-function variants in IL10RB are known to be pathogenic (PMID: 22549091). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
ClinPred
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at