11-118001371-G-A

Position:

• chr11-118001371-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001558.4(IL10RA):​c.*1730G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 453,704 control chromosomes in the GnomAD database, including 57,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21482 hom., cov: 32)
  • Exomes 𝑓: 0.48 (36165 hom.)
• Consequence: IL10RA NM_001558.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.10

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-118001371-G-A is Benign according to our data. Variant chr11-118001371-G-A is described in ClinVar as [Benign]. Clinvar id is 302580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RA	NM_001558.4	c.*1730G>A		3_prime_UTR_variant	7/7	ENST00000227752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8	c.*1730G>A		3_prime_UTR_variant	7/7	1	NM_001558.4	P1
IL10RA	ENST00000529924.6	n.5045G>A		non_coding_transcript_exon_variant	6/6	1
IL10RA	ENST00000525467.2	n.5254G>A		non_coding_transcript_exon_variant	6/6	2
IL10RA	ENST00000696732.1	n.5316G>A		non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79466 AN: 151802 Hom.: 21456 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.513 AC: 65794 AN: 128258 Hom.: 17290 AF XY: 0.506 AC XY: 35514 AN XY: 70230

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.508

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.449

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.483 AC: 145903 AN: 301784 Hom.: 36165 Cov.: 0 AF XY: 0.483 AC XY: 82999 AN XY: 171972

Gnomad4 AFR exome AF: 0.648

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.524 AC: 79545 AN: 151920 Hom.: 21482 Cov.: 32 AF XY: 0.525 AC XY: 38968 AN XY: 74252

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.541

Alfa AF: 0.474 Hom.: 24808

Bravo AF: 0.543

Asia WGS AF: 0.583 AC: 2022 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inflammatory bowel disease 28 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.049
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs9610; hg19: chr11-117872086;