rs8178561

Variant names:

• chr21-33296492-G-A
• rs8178561
• NM_000628.5:c.*135G>A

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.*135G>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 0.0582 in 850,424 control chromosomes in the GnomAD database, including 1,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (642 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1251 hom.)
• Consequence: IL10RB NM_000628.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.190
• Publications: 8 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=-0.9).
• BP6: Variant 21-33296492-G-A is Benign according to our data. Variant chr21-33296492-G-A is described in ClinVar as Benign. ClinVar VariationId is 339699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.*135G>A		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.*135G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.*135G>A		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11982 AN: 152092 Hom.: 635 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0868

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0746

GnomAD2 exomes AF: 0.0483 AC: 6733 AN: 139398 AF XY: 0.0452

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.00115

Gnomad FIN exome AF: 0.0510

Gnomad NFE exome AF: 0.0597

Gnomad OTH exome AF: 0.0561

GnomAD4 exome AF: 0.0536 AC: 37454 AN: 698214 Hom.: 1251 Cov.: 9 AF XY: 0.0508 AC XY: 18776 AN XY: 369298

African (AFR) AF: 0.142 AC: 2627 AN: 18524

American (AMR) AF: 0.0382 AC: 1336 AN: 35012

Ashkenazi Jewish (ASJ) AF: 0.0903 AC: 1889 AN: 20928

East Asian (EAS) AF: 0.000579 AC: 19 AN: 32792

South Asian (SAS) AF: 0.0118 AC: 782 AN: 66132

European-Finnish (FIN) AF: 0.0479 AC: 1644 AN: 34292

Middle Eastern (MID) AF: 0.0634 AC: 276 AN: 4350

European-Non Finnish (NFE) AF: 0.0589 AC: 26575 AN: 450816

Other (OTH) AF: 0.0652 AC: 2306 AN: 35368

GnomAD4 genome AF: 0.0789 AC: 12015 AN: 152210 Hom.: 642 Cov.: 32 AF XY: 0.0776 AC XY: 5772 AN XY: 74418

African (AFR) AF: 0.141 AC: 5866 AN: 41514

American (AMR) AF: 0.0575 AC: 879 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 301 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4826

European-Finnish (FIN) AF: 0.0538 AC: 570 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4141 AN: 68018

Other (OTH) AF: 0.0771 AC: 163 AN: 2114

Alfa AF: 0.0720 Hom.: 744

Bravo AF: 0.0816

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	-0.90
CADD	Benign	1.8
DANN	Benign	0.28
PhyloP100		-0.19
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: rs8178561; hg19: chr21-34668797;