rs9610

Variant names:

• chr11-118001371-G-A
• rs9610
• ENST00000529924.6:n.5045G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-118001371-G-A
• chr11-118001371-G-T

Variant summary

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

The ENST00000529924.6(IL10RA):​n.5045G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 453,704 control chromosomes in the GnomAD database, including 57,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21482 hom., cov: 32)
  • Exomes 𝑓: 0.48 (36165 hom.)
• Consequence: IL10RA ENST00000529924.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.10
• Publications: 49 publications found

Genes affected

IL10RA (HGNC:5964): (interleukin 10 receptor subunit alpha) The protein encoded by this gene is a receptor for interleukin 10. This protein is structurally related to interferon receptors. It has been shown to mediate the immunosuppressive signal of interleukin 10, and thus inhibits the synthesis of proinflammatory cytokines. This receptor is reported to promote survival of progenitor myeloid cells through the insulin receptor substrate-2/PI 3-kinase/AKT pathway. Activation of this receptor leads to tyrosine phosphorylation of JAK1 and TYK2 kinases. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2009]

IL10RA Gene-Disease associations (from GenCC):

• inflammatory bowel disease 28

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-118001371-G-A is Benign according to our data. Variant chr11-118001371-G-A is described in ClinVar as Benign. ClinVar VariationId is 302580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.*1730G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000529924.6	n.5045G>A		non_coding_transcript_exon_variant	Exon 6 of 6	1
IL10RA	ENST00000227752.8	c.*1730G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001558.4	ENSP00000227752.4
IL10RA	ENST00000525467.2	n.5254G>A		non_coding_transcript_exon_variant	Exon 6 of 6	2
IL10RA	ENST00000696732.1	n.5316G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79466 AN: 151802 Hom.: 21456 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.543

GnomAD2 exomes AF: 0.513 AC: 65794 AN: 128258 AF XY: 0.506

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.449

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.483 AC: 145903 AN: 301784 Hom.: 36165 Cov.: 0 AF XY: 0.483 AC XY: 82999 AN XY: 171972

African (AFR) AF: 0.648 AC: 5538 AN: 8550

American (AMR) AF: 0.605 AC: 16486 AN: 27270

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 5117 AN: 10786

East Asian (EAS) AF: 0.600 AC: 5599 AN: 9326

South Asian (SAS) AF: 0.502 AC: 29956 AN: 59646

European-Finnish (FIN) AF: 0.406 AC: 5015 AN: 12366

Middle Eastern (MID) AF: 0.528 AC: 607 AN: 1150

European-Non Finnish (NFE) AF: 0.446 AC: 70685 AN: 158652

Other (OTH) AF: 0.492 AC: 6900 AN: 14038

GnomAD4 genome AF: 0.524 AC: 79545 AN: 151920 Hom.: 21482 Cov.: 32 AF XY: 0.525 AC XY: 38968 AN XY: 74252

African (AFR) AF: 0.651 AC: 26972 AN: 41420

American (AMR) AF: 0.575 AC: 8782 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3046 AN: 5162

South Asian (SAS) AF: 0.522 AC: 2513 AN: 4814

European-Finnish (FIN) AF: 0.392 AC: 4135 AN: 10536

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.450 AC: 30579 AN: 67936

Other (OTH) AF: 0.541 AC: 1140 AN: 2106

Alfa AF: 0.481 Hom.: 35041

Bravo AF: 0.543

Asia WGS AF: 0.583 AC: 2022 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inflammatory bowel disease 28 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.049
DANN	Benign	0.39
PhyloP100		-2.1
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: rs9610; hg19: chr11-117872086;