rs4252279

Variant names:

• chr11-117996472-C-T
• rs4252279
• NM_001558.4:c.810+762C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001558.4(IL10RA):​c.810+762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,300 control chromosomes in the GnomAD database, including 871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (871 hom., cov: 33)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 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.810+762C>T		intron	N/A	NP_001549.2	Q13651
	IL10RA	NM_001440423.1		c.363+762C>T		intron	N/A	NP_001427352.1
	IL10RA	NR_026691.2		n.1014+762C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.810+762C>T		intron	N/A	ENSP00000227752.4	Q13651
	IL10RA	ENST00000529924.6	TSL:1	n.2388+762C>T		intron	N/A
	IL10RA	ENST00000951964.1		c.804+762C>T		intron	N/A	ENSP00000622023.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15747 AN: 152182 Hom.: 866 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0929

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15775 AN: 152300 Hom.: 871 Cov.: 33 AF XY: 0.103 AC XY: 7692 AN XY: 74474

African (AFR) AF: 0.0921 AC: 3827 AN: 41548

American (AMR) AF: 0.141 AC: 2152 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.0555 AC: 288 AN: 5188

South Asian (SAS) AF: 0.102 AC: 494 AN: 4830

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10618

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7138 AN: 68024

Other (OTH) AF: 0.0972 AC: 205 AN: 2110

Alfa AF: 0.106 Hom.: 176

Bravo AF: 0.105

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		0.35
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: rs4252279; hg19: chr11-117867187;