chr11-117993332-A-G

Variant names:

• chr11-117993332-A-G
• rs2256111
• NM_001558.4:c.459A>G

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.459A>G​(p.Ala153Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,613,002 control chromosomes in the GnomAD database, including 217,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19804 hom., cov: 32)
  • Exomes 𝑓: 0.52 (197547 hom.)
• Consequence: IL10RA NM_001558.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: -0.00400
• Publications: 36 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=-0.83).
• BP6: Variant 11-117993332-A-G is Benign according to our data. Variant chr11-117993332-A-G is described in ClinVar as Benign. ClinVar VariationId is 302546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001558.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	NM_001558.4	MANE Select	c.459A>G	p.Ala153Ala	synonymous	Exon 4 of 7	NP_001549.2
	IL10RA	NM_001440423.1		c.12A>G	p.Ala4Ala	synonymous	Exon 2 of 5	NP_001427352.1
	IL10RA	NR_026691.2		n.663A>G		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.459A>G	p.Ala153Ala	synonymous	Exon 4 of 7	ENSP00000227752.4
	IL10RA	ENST00000529924.6	TSL:1	n.2037A>G		non_coding_transcript_exon	Exon 3 of 6
	IL10RA	ENST00000525467.2	TSL:2	n.807A>G		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77087 AN: 152008 Hom.: 19784 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.543

GnomAD2 exomes AF: 0.533 AC: 133968 AN: 251408 AF XY: 0.530

Gnomad AFR exome AF: 0.453

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.615

Gnomad FIN exome AF: 0.443

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.537

GnomAD4 exome AF: 0.518 AC: 757086 AN: 1460876 Hom.: 197547 Cov.: 38 AF XY: 0.518 AC XY: 376478 AN XY: 726810

African (AFR) AF: 0.453 AC: 15157 AN: 33470

American (AMR) AF: 0.616 AC: 27568 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 14804 AN: 26124

East Asian (EAS) AF: 0.560 AC: 22236 AN: 39688

South Asian (SAS) AF: 0.525 AC: 45307 AN: 86236

European-Finnish (FIN) AF: 0.451 AC: 24085 AN: 53416

Middle Eastern (MID) AF: 0.578 AC: 3333 AN: 5766

European-Non Finnish (NFE) AF: 0.515 AC: 572693 AN: 1111096

Other (OTH) AF: 0.529 AC: 31903 AN: 60358

GnomAD4 genome AF: 0.507 AC: 77144 AN: 152126 Hom.: 19804 Cov.: 32 AF XY: 0.507 AC XY: 37730 AN XY: 74374

African (AFR) AF: 0.459 AC: 19030 AN: 41466

American (AMR) AF: 0.578 AC: 8838 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3111 AN: 5188

South Asian (SAS) AF: 0.533 AC: 2570 AN: 4822

European-Finnish (FIN) AF: 0.437 AC: 4621 AN: 10582

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35132 AN: 67988

Other (OTH) AF: 0.540 AC: 1140 AN: 2112

Alfa AF: 0.518 Hom.: 63478

Bravo AF: 0.517

Asia WGS AF: 0.577 AC: 2004 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.523

ClinVar

Significance: Benign

Submissions summary: Benign:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 77. Only high quality variants are reported.

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

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 12, 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 Other:1

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2256111; hg19: chr11-117864047; COSMIC: COSV57140815; COSMIC: COSV57140815;