rs3171425

Variant names:

• chr21-33296442-A-G
• rs3171425
• NM_000628.5:c.*85A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-33296442-A-G
• chr21-33296442-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000628.5(IL10RB):​c.*85A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,352,454 control chromosomes in the GnomAD database, including 241,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23192 hom., cov: 31)
  • Exomes 𝑓: 0.60 (218368 hom.)
• Consequence: IL10RB NM_000628.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.29
• Publications: 28 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-33296442-A-G is Benign according to our data. Variant chr21-33296442-A-G is described in ClinVar as Benign. ClinVar VariationId is 339698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.*85A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.*85A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.*85A>G		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81818 AN: 151914 Hom.: 23200 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.557

GnomAD2 exomes AF: 0.603 AC: 112453 AN: 186518 AF XY: 0.606

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.611

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.745

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.595

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.601 AC: 721012 AN: 1200422 Hom.: 218368 Cov.: 16 AF XY: 0.603 AC XY: 365803 AN XY: 606570

African (AFR) AF: 0.350 AC: 9896 AN: 28250

American (AMR) AF: 0.602 AC: 23391 AN: 38842

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 11393 AN: 24250

East Asian (EAS) AF: 0.763 AC: 28024 AN: 36708

South Asian (SAS) AF: 0.661 AC: 52126 AN: 78890

European-Finnish (FIN) AF: 0.652 AC: 25024 AN: 38382

Middle Eastern (MID) AF: 0.554 AC: 2932 AN: 5296

European-Non Finnish (NFE) AF: 0.598 AC: 537204 AN: 897802

Other (OTH) AF: 0.597 AC: 31022 AN: 52002

GnomAD4 genome AF: 0.538 AC: 81819 AN: 152032 Hom.: 23192 Cov.: 31 AF XY: 0.544 AC XY: 40384 AN XY: 74302

African (AFR) AF: 0.358 AC: 14843 AN: 41470

American (AMR) AF: 0.583 AC: 8895 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3874 AN: 5164

South Asian (SAS) AF: 0.671 AC: 3227 AN: 4812

European-Finnish (FIN) AF: 0.655 AC: 6921 AN: 10574

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40478 AN: 67960

Other (OTH) AF: 0.558 AC: 1180 AN: 2114

Alfa AF: 0.568 Hom.: 33326

Bravo AF: 0.525

Asia WGS AF: 0.708 AC: 2463 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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 76% of patients studied by a panel of primary immunodeficiencies. Number of patients: 73. Only high quality variants are reported. -

Inflammatory bowel disease 25 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.45
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3171425; hg19: chr21-34668747; COSMIC: COSV51615622; COSMIC: COSV51615622;