chr21-33266466-A-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000628.5(IL10RB):​c.1A>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

IL10RB
NM_000628.5 start_lost

Scores

3
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.169
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Start lost variant, no new inframe start found.
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.1A>C p.Met1? start_lost 1/7 ENST00000290200.7 NP_000619.3
IFNAR2-IL10RBNM_001414505.1 linkuse as main transcriptc.710-1928A>C intron_variant NP_001401434.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL10RBENST00000290200.7 linkuse as main transcriptc.1A>C p.Met1? start_lost 1/71 NM_000628.5 ENSP00000290200 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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), LabcorpApr 08, 2021In 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with IL10RB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the IL10RB mRNA. The next in-frame methionine is located at codon 20. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
16
DANN
Benign
0.72
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.079
N
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.65
N
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.071
B
Vest4
0.72
MutPred
0.95
Loss of MoRF binding (P = 0.0735);
MVP
0.34
ClinPred
0.85
D
GERP RS
1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.61
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-34638771; API