rs2228054

chr11-117993398-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001558.4(IL10RA):c.525G>A(p.Pro175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,613,958 control chromosomes in the GnomAD database, including 6,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (508 hom., cov: 33)
  • Exomes 𝑓: 0.067 (5704 hom.)
• Consequence: IL10RA NM_001558.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.65

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-117993398-G-A is Benign according to our data. Variant chr11-117993398-G-A is described in ClinVar as [Benign]. Clinvar id is 302547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117993398-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RA	NM_001558.4	c.525G>A	p.Pro175=	synonymous_variant	4/7	ENST00000227752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8	c.525G>A	p.Pro175=	synonymous_variant	4/7	1	NM_001558.4	P1

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8479 AN: 152192 Hom.: 508 Cov.: 33

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0536

GnomAD3 exomes AF: 0.0830 AC: 20866 AN: 251412 Hom.: 1610 AF XY: 0.0833 AC XY: 11318 AN XY: 135888

Gnomad AFR exome AF: 0.0100

Gnomad AMR exome AF: 0.0779

Gnomad ASJ exome AF: 0.0674

Gnomad EAS exome AF: 0.330

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.0583

Gnomad NFE exome AF: 0.0547

Gnomad OTH exome AF: 0.0702

GnomAD4 exome AF: 0.0667 AC: 97491 AN: 1461646 Hom.: 5704 Cov.: 34 AF XY: 0.0680 AC XY: 49464 AN XY: 727124

Gnomad4 AFR exome AF: 0.00887

Gnomad4 AMR exome AF: 0.0747

Gnomad4 ASJ exome AF: 0.0678

Gnomad4 EAS exome AF: 0.373

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0540

Gnomad4 OTH exome AF: 0.0741

GnomAD4 genome AF: 0.0557 AC: 8478 AN: 152312 Hom.: 508 Cov.: 33 AF XY: 0.0588 AC XY: 4383 AN XY: 74482

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0711

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0556 Hom.: 338

Bravo AF: 0.0528

Asia WGS AF: 0.198 AC: 689 AN: 3478

EpiCase AF: 0.0559

EpiControl AF: 0.0577

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inflammatory bowel disease 28 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	-0.87
Cadd	Benign	0.24
Dann	Benign	0.55

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: rs2228054; hg19: chr11-117864113; COSMIC: COSV57141473; COSMIC: COSV57141473;