rs4252249

Variant names:

• chr11-117988494-G-A
• rs4252249
• NM_001558.4:c.180G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-117988494-G-A
• chr11-117988494-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001558.4(IL10RA):​c.180G>A​(p.Ala60Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,030 control chromosomes in the GnomAD database, including 10,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1261 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9155 hom.)
• Consequence: IL10RA NM_001558.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.816
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-117988494-G-A is Benign according to our data. Variant chr11-117988494-G-A is described in ClinVar as Benign. ClinVar VariationId is 302538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.816 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.180G>A	p.Ala60Ala	synonymous_variant	Exon 2 of 7	ENST00000227752.8	NP_001549.2
IL10RA	XM_047426882.1	c.120G>A	p.Ala40Ala	synonymous_variant	Exon 2 of 7		XP_047282838.1
IL10RA	NR_026691.2	n.384G>A		non_coding_transcript_exon_variant	Exon 3 of 8
IL10RA	XM_047426884.1	c.-89G>A		5_prime_UTR_variant	Exon 1 of 5		XP_047282840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.180G>A	p.Ala60Ala	synonymous_variant	Exon 2 of 7	1	NM_001558.4	ENSP00000227752.4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18825 AN: 151962 Hom.: 1252 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.115 AC: 28935 AN: 251442 AF XY: 0.112

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.0807

Gnomad EAS exome AF: 0.0507

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.110 AC: 160273 AN: 1460950 Hom.: 9155 Cov.: 33 AF XY: 0.109 AC XY: 78926 AN XY: 726812

African (AFR) AF: 0.161 AC: 5374 AN: 33446

American (AMR) AF: 0.186 AC: 8310 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 2206 AN: 26132

East Asian (EAS) AF: 0.0647 AC: 2567 AN: 39684

South Asian (SAS) AF: 0.101 AC: 8740 AN: 86238

European-Finnish (FIN) AF: 0.114 AC: 6063 AN: 53398

Middle Eastern (MID) AF: 0.0784 AC: 452 AN: 5768

European-Non Finnish (NFE) AF: 0.108 AC: 120256 AN: 1111208

Other (OTH) AF: 0.104 AC: 6305 AN: 60356

GnomAD4 genome AF: 0.124 AC: 18860 AN: 152080 Hom.: 1261 Cov.: 32 AF XY: 0.123 AC XY: 9146 AN XY: 74338

African (AFR) AF: 0.155 AC: 6427 AN: 41452

American (AMR) AF: 0.167 AC: 2557 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3470

East Asian (EAS) AF: 0.0562 AC: 290 AN: 5164

South Asian (SAS) AF: 0.103 AC: 499 AN: 4828

European-Finnish (FIN) AF: 0.124 AC: 1309 AN: 10592

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7176 AN: 67982

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.112 Hom.: 1758

Bravo AF: 0.129

Asia WGS AF: 0.0820 AC: 287 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.103

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inflammatory bowel disease 28 Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 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 30% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

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	-0.86
CADD	Benign	3.8
DANN	Benign	0.68
PhyloP100		-0.82
Mutation Taster		=300/0	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: rs4252249; hg19: chr11-117859209; COSMIC: COSV57142345; COSMIC: COSV57142345;