rs2229113

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42313 hom., cov: 33)

Exomes 𝑓: 0.70 ( 364466 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.0510

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 302554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117998955-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4 link	c.1051A>G	p.Arg351Gly	missense_variant	7/7	ENST00000227752.8	NP_001549.2	Q13651

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 link	c.1051A>G	p.Arg351Gly	missense_variant	7/7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112610

AN:

152016

Hom.:

42261

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.743

AC:

186430

AN:

250854

Hom.:

70678

AF XY:

0.735

AC XY:

99685

AN XY:

135580

show subpopulations

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 SAS exome

AF:

0.738

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.:

AF XY:

0.702

AC XY:

510298

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.805

Gnomad4 AMR exome

AF:

0.859

Gnomad4 ASJ exome

AF:

0.733

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.733

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.741

AC:

112720

AN:

152134

Hom.:

42313

Cov.:

AF XY:

0.741

AC XY:

55104

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.804

Gnomad4 AMR

AF:

0.811

Gnomad4 ASJ

AF:

0.735

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.745

Gnomad4 FIN

AF:

0.628

Gnomad4 NFE

AF:

0.685

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.704

Hom.:

68148

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

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2019	This variant is associated with the following publications: (PMID: 17066477, 19772791, 19016528, 18800073, 21654841, 24595243, 23455702, 12759436, 29248579) -

Inflammatory bowel disease 28

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.3

DANN

Benign

0.62

DEOGEN2

Benign

0.075

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.18

MetaRNN

Benign

8.2e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

PrimateAI

Benign

0.25

PROVEAN

Benign

0.57

REVEL

Benign

0.029

Sift

Benign

0.68

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.010

MPC

0.27

ClinPred

0.00043

GERP RS

1.1

Varity_R

0.036

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over