11-117991583-A-G

Variant names:

• chr11-117991583-A-G
• rs2512144
• NM_001558.4:c.368-1658A>G

Variant summary

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

The NM_001558.4(IL10RA):​c.368-1658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,984 control chromosomes in the GnomAD database, including 37,485 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 0.70 (37485 hom., cov: 31)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.368-1658A>G		intron_variant	Intron 3 of 6	ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.368-1658A>G		intron_variant	Intron 3 of 6	1	NM_001558.4	ENSP00000227752.4

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106041 AN: 151866 Hom.: 37452 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.698 AC: 106115 AN: 151984 Hom.: 37485 Cov.: 31 AF XY: 0.700 AC XY: 51998 AN XY: 74292

African (AFR) AF: 0.678 AC: 28086 AN: 41438

American (AMR) AF: 0.790 AC: 12080 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5155 AN: 5184

South Asian (SAS) AF: 0.745 AC: 3577 AN: 4804

European-Finnish (FIN) AF: 0.622 AC: 6552 AN: 10542

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45823 AN: 67936

Other (OTH) AF: 0.715 AC: 1509 AN: 2110

Alfa AF: 0.690 Hom.: 42386

Bravo AF: 0.712

Asia WGS AF: 0.856 AC: 2974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.80
PhyloP100		-0.64
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: rs2512144; hg19: chr11-117862298;