21-33266484-AGCTGGCTGGGTGGCTGCCT-A

Variant names:

• chr21-33266484-AGCTGGCTGGGTGGCTGCCT-A
• NM_000628.5:c.25_43delCTGGGTGGCTGCCTGCTGG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_000628.5(IL10RB):​c.25_43delCTGGGTGGCTGCCTGCTGG​(p.Leu9CysfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L9L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL10RB NM_000628.5 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.62
• Publications: 1 publications found

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]

IFNAR2-IL10RB (HGNC:):

IL10RB-DT (HGNC:44303): (IL10RB divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
• PP5: Variant 21-33266484-AGCTGGCTGGGTGGCTGCCT-A is Pathogenic according to our data. Variant chr21-33266484-AGCTGGCTGGGTGGCTGCCT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2664350.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.25_43delCTGGGTGGCTGCCTGCTGG	p.Leu9CysfsTer15	frameshift_variant	Exon 1 of 7	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.25_43delCTGGGTGGCTGCCTGCTGG	p.Leu9CysfsTer15	frameshift_variant	Exon 1 of 7	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.710-1904_710-1886delCTGGGTGGCTGCCTGCTGG		intron_variant	Intron 7 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Inflammatory bowel disease 25 Pathogenic:1

Dec 04, 2023

Clinical Bioinformatic Lab, Royan Institute

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

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

Other links and lift over

hg19: chr21-34638789;