chr11-117988494-G-A

Variant names:

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

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	NM_001558.4	MANE Select	c.180G>A	p.Ala60Ala	synonymous	Exon 2 of 7	NP_001549.2
	IL10RA	NR_026691.2		n.384G>A		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.180G>A	p.Ala60Ala	synonymous	Exon 2 of 7	ENSP00000227752.4
	IL10RA	ENST00000529924.6	TSL:1	n.1758G>A		non_coding_transcript_exon	Exon 1 of 6
	IL10RA	ENST00000951964.1		c.174G>A	p.Ala58Ala	synonymous	Exon 2 of 7	ENSP00000622023.1

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Inflammatory bowel disease 28 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;