NM_000628.5:c.*85A>G

Variant names:

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	NM_000628.5	MANE Select	c.*85A>G		3_prime_UTR	Exon 7 of 7	NP_000619.3
	IFNAR2-IL10RB	NM_001414505.1		c.*85A>G		3_prime_UTR	Exon 13 of 13	NP_001401434.1
	IL10RB	NM_001406840.1		c.*236A>G		3_prime_UTR	Exon 6 of 6	NP_001393769.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.*85A>G		3_prime_UTR	Exon 7 of 7	ENSP00000290200.2
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.*85A>G		3_prime_UTR	Exon 13 of 13	ENSP00000388223.3
	IL10RB	ENST00000896213.1		c.*85A>G		3_prime_UTR	Exon 7 of 7	ENSP00000566272.1

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inflammatory bowel disease 25 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;