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. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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

GnomAD3 exomes AF: 0.603 AC: 112453 AN: 186518 Hom.: 34253 AF XY: 0.606 AC XY: 61961 AN XY: 102170

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 SAS exome AF: 0.666

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

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.763

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.597

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

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.558

Alfa AF: 0.574 Hom.: 26104

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs3171425; hg19: chr21-34668747; COSMIC: COSV51615622; COSMIC: COSV51615622;