NM_000628.5:c.49+40G>A

Variant names:

• chr21-33266554-G-A
• rs2239573
• NM_000628.5:c.49+40G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000628.5(IL10RB):​c.49+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,535,164 control chromosomes in the GnomAD database, including 368,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31879 hom., cov: 32)
  • Exomes 𝑓: 0.70 (336520 hom.)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123
• Publications: 15 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]

IL10RB Gene-Disease associations (from GenCC):

• inflammatory bowel disease 25

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFNAR2-IL10RB (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 21-33266554-G-A is Benign according to our data. Variant chr21-33266554-G-A is described in ClinVar as [Benign]. Clinvar id is 2628110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.49+40G>A		intron_variant	Intron 1 of 6	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.49+40G>A		intron_variant	Intron 1 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.710-1840G>A		intron_variant	Intron 7 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96878 AN: 151948 Hom.: 31871 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.652

GnomAD2 exomes AF: 0.682 AC: 94397 AN: 138502 AF XY: 0.687

Gnomad AFR exome AF: 0.461

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.740

Gnomad EAS exome AF: 0.767

Gnomad FIN exome AF: 0.730

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.673

GnomAD4 exome AF: 0.696 AC: 962292 AN: 1383098 Hom.: 336520 Cov.: 31 AF XY: 0.697 AC XY: 475993 AN XY: 682854

African (AFR) AF: 0.464 AC: 14580 AN: 31396

American (AMR) AF: 0.624 AC: 22264 AN: 35662

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 18596 AN: 25112

East Asian (EAS) AF: 0.753 AC: 26859 AN: 35670

South Asian (SAS) AF: 0.665 AC: 52548 AN: 79006

European-Finnish (FIN) AF: 0.731 AC: 27800 AN: 38024

Middle Eastern (MID) AF: 0.641 AC: 3309 AN: 5162

European-Non Finnish (NFE) AF: 0.704 AC: 756569 AN: 1075348

Other (OTH) AF: 0.689 AC: 39767 AN: 57718

GnomAD4 genome AF: 0.637 AC: 96927 AN: 152066 Hom.: 31879 Cov.: 32 AF XY: 0.640 AC XY: 47622 AN XY: 74354

African (AFR) AF: 0.468 AC: 19409 AN: 41486

American (AMR) AF: 0.625 AC: 9555 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2526 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3952 AN: 5150

South Asian (SAS) AF: 0.666 AC: 3204 AN: 4810

European-Finnish (FIN) AF: 0.733 AC: 7758 AN: 10590

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48551 AN: 67948

Other (OTH) AF: 0.650 AC: 1375 AN: 2114

Alfa AF: 0.675 Hom.: 14899

Bravo AF: 0.624

Asia WGS AF: 0.679 AC: 2360 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.85
PhyloP100		0.12
PromoterAI		0.37	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2239573; hg19: chr21-34638859;