21-33266500-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000628.5(IL10RB):​c.35G>A​(p.Cys12Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,390,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

IL10RB
NM_000628.5 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL10RBNM_000628.5 linkuse as main transcriptc.35G>A p.Cys12Tyr missense_variant 1/7 ENST00000290200.7 NP_000619.3
IFNAR2-IL10RBNM_001414505.1 linkuse as main transcriptc.710-1894G>A intron_variant NP_001401434.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL10RBENST00000290200.7 linkuse as main transcriptc.35G>A p.Cys12Tyr missense_variant 1/71 NM_000628.5 ENSP00000290200 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000288
AC:
4
AN:
1390586
Hom.:
0
Cov.:
31
AF XY:
0.00000291
AC XY:
2
AN XY:
686402
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inflammatory bowel disease 25 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 20, 2021This sequence change replaces cysteine with tyrosine at codon 12 of the IL10RB protein (p.Cys12Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with IL10RB-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.54
D
Eigen
Benign
0.14
Eigen_PC
Benign
0.089
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.61
T
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.56
D
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
0.98
N
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.17
Sift
Benign
0.057
T
Sift4G
Benign
0.077
T
Polyphen
0.73
P
Vest4
0.49
MutPred
0.71
Loss of catalytic residue at L13 (P = 0.0309);
MVP
0.79
MPC
0.55
ClinPred
0.94
D
GERP RS
2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1988945494; hg19: chr21-34638805; COSMIC: COSV51614071; COSMIC: COSV51614071; API