rs2229113

Variant names:

• chr11-117998955-A-G
• rs2229113
• NM_001558.4:c.1051A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-117998955-A-G
• chr11-117998955-A-T

Variant summary

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

The NM_001558.4(IL10RA):​c.1051A>G​(p.Arg351Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,612,978 control chromosomes in the GnomAD database, including 406,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (42313 hom., cov: 33)
  • Exomes 𝑓: 0.70 (364466 hom.)
• Consequence: IL10RA NM_001558.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: 0.0510
• Publications: 73 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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• 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 (MetaRNN=8.1809E-7).
• BP6: Variant 11-117998955-A-G is Benign according to our data. Variant chr11-117998955-A-G is described in ClinVar as Benign. ClinVar VariationId is 302554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.1051A>G	p.Arg351Gly	missense	Exon 7 of 7	NP_001549.2	Q13651
	IL10RA	NM_001440423.1		c.604A>G	p.Arg202Gly	missense	Exon 5 of 5	NP_001427352.1
	IL10RA	NR_026691.2		n.1255A>G		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.1051A>G	p.Arg351Gly	missense	Exon 7 of 7	ENSP00000227752.4	Q13651
	IL10RA	ENST00000529924.6	TSL:1	n.2629A>G		non_coding_transcript_exon	Exon 6 of 6
	IL10RA	ENST00000951964.1		c.1045A>G	p.Arg349Gly	missense	Exon 7 of 7	ENSP00000622023.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112610 AN: 152016 Hom.: 42261 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.749

GnomAD2 exomes AF: 0.743 AC: 186430 AN: 250854 AF XY: 0.735

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.866

Gnomad ASJ exome AF: 0.732

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.622

Gnomad NFE exome AF: 0.682

Gnomad OTH exome AF: 0.728

GnomAD4 exome AF: 0.703 AC: 1027034 AN: 1460844 Hom.: 364466 Cov.: 60 AF XY: 0.702 AC XY: 510298 AN XY: 726520

African (AFR) AF: 0.805 AC: 26916 AN: 33456

American (AMR) AF: 0.859 AC: 38405 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 19161 AN: 26124

East Asian (EAS) AF: 0.998 AC: 39584 AN: 39670

South Asian (SAS) AF: 0.733 AC: 63198 AN: 86242

European-Finnish (FIN) AF: 0.627 AC: 33392 AN: 53298

Middle Eastern (MID) AF: 0.719 AC: 4138 AN: 5758

European-Non Finnish (NFE) AF: 0.683 AC: 758665 AN: 1111252

Other (OTH) AF: 0.722 AC: 43575 AN: 60338

GnomAD4 genome AF: 0.741 AC: 112720 AN: 152134 Hom.: 42313 Cov.: 33 AF XY: 0.741 AC XY: 55104 AN XY: 74352

African (AFR) AF: 0.804 AC: 33374 AN: 41528

American (AMR) AF: 0.811 AC: 12412 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2549 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5141 AN: 5170

South Asian (SAS) AF: 0.745 AC: 3591 AN: 4818

European-Finnish (FIN) AF: 0.628 AC: 6634 AN: 10564

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46571 AN: 67960

Other (OTH) AF: 0.751 AC: 1589 AN: 2116

Alfa AF: 0.708 Hom.: 94230

Bravo AF: 0.760

TwinsUK AF: 0.689 AC: 2554

ALSPAC AF: 0.676 AC: 2607

ESP6500AA AF: 0.808 AC: 3556

ESP6500EA AF: 0.688 AC: 5908

ExAC AF: 0.738 AC: 89558

Asia WGS AF: 0.867 AC: 3011 AN: 3478

EpiCase AF: 0.694

EpiControl AF: 0.692

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Inflammatory bowel disease 28 (2)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.3
DANN	Benign	0.62
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	8.2e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.051
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.029
Sift	Benign	0.68	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.010
MPC		0.27
ClinPred		0.00043	T
GERP RS		1.1
Varity_R		0.036
gMVP		0.17
Mutation Taster		=98/2	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: rs2229113; hg19: chr11-117869670; COSMIC: COSV57142373; COSMIC: COSV57142373;