rs1058867

Variant names:

• chr21-33297076-G-A
• rs1058867
• NM_000628.5:c.*719G>A

Variant summary

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

The NM_001414505.1(IFNAR2-IL10RB):​c.*719G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 160,450 control chromosomes in the GnomAD database, including 24,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23022 hom., cov: 30)
  • Exomes 𝑓: 0.59 (1613 hom.)
• Consequence: IFNAR2-IL10RB NM_001414505.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.660
• Publications: 37 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=-0.91).
• BP6: Variant 21-33297076-G-A is Benign according to our data. Variant chr21-33297076-G-A is described in ClinVar as Benign. ClinVar VariationId is 339709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414505.1. 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.*719G>A		3_prime_UTR	Exon 7 of 7	NP_000619.3
	IFNAR2-IL10RB	NM_001414505.1		c.*719G>A		3_prime_UTR	Exon 13 of 13	NP_001401434.1
	IL10RB	NM_001406840.1		c.*870G>A		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.*719G>A		3_prime_UTR	Exon 7 of 7	ENSP00000290200.2
	IL10RB	ENST00000896213.1		c.*719G>A		3_prime_UTR	Exon 7 of 7	ENSP00000566272.1
	IL10RB	ENST00000896212.1		c.*719G>A		3_prime_UTR	Exon 7 of 7	ENSP00000566271.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81495 AN: 151690 Hom.: 23031 Cov.: 30

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.592 AC: 5116 AN: 8642 Hom.: 1613 Cov.: 0 AF XY: 0.588 AC XY: 2603 AN XY: 4426

African (AFR) AF: 0.167 AC: 7 AN: 42

American (AMR) AF: 0.598 AC: 973 AN: 1628

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 28 AN: 62

East Asian (EAS) AF: 0.670 AC: 264 AN: 394

South Asian (SAS) AF: 0.655 AC: 642 AN: 980

European-Finnish (FIN) AF: 0.559 AC: 66 AN: 118

Middle Eastern (MID) AF: 0.400 AC: 4 AN: 10

European-Non Finnish (NFE) AF: 0.579 AC: 2929 AN: 5058

Other (OTH) AF: 0.580 AC: 203 AN: 350

GnomAD4 genome AF: 0.537 AC: 81494 AN: 151808 Hom.: 23022 Cov.: 30 AF XY: 0.542 AC XY: 40195 AN XY: 74174

African (AFR) AF: 0.357 AC: 14774 AN: 41340

American (AMR) AF: 0.581 AC: 8870 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3470

East Asian (EAS) AF: 0.746 AC: 3860 AN: 5172

South Asian (SAS) AF: 0.663 AC: 3188 AN: 4812

European-Finnish (FIN) AF: 0.655 AC: 6867 AN: 10486

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40356 AN: 67932

Other (OTH) AF: 0.557 AC: 1179 AN: 2116

Alfa AF: 0.570 Hom.: 79513

Bravo AF: 0.524

Asia WGS AF: 0.705 AC: 2451 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.51
PhyloP100		-0.66
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: rs1058867; hg19: chr21-34669381;