11-117993348-A-G

Position:

chr11-117993348-A-G

Variant summary

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

The NM_001558.4(IL10RA):c.475A>G(p.Ser159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,704 control chromosomes in the GnomAD database, including 20,461 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1413 hom., cov: 33)

Exomes 𝑓: 0.15 ( 19048 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.415

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:

IL10RA (HGNC:):

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=0.0017890036).

BP6

Variant 11-117993348-A-G is Benign according to our data. Variant chr11-117993348-A-G is described in ClinVar as [Benign]. Clinvar id is 197197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117993348-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4 linkuse as main transcript	c.475A>G	p.Ser159Gly	missense_variant	4/7	ENST00000227752.8	NP_001549.2	Q13651

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.475A>G	p.Ser159Gly	missense_variant	4/7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17411

AN:

152176

Hom.:

1415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0730

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.00403

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.130

AC:

32588

AN:

251430

Hom.:

2721

AF XY:

0.136

AC XY:

18539

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.0519

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.00218

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.154

AC:

225212

AN:

1461410

Hom.:

19048

Cov.:

AF XY:

0.155

AC XY:

113025

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.0550

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.000806

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.114

AC:

17399

AN:

152294

Hom.:

1413

Cov.:

AF XY:

0.115

AC XY:

8546

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.0728

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.00404

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.147

Hom.:

3692

Bravo

AF:

0.0976

TwinsUK

AF:

0.166

AC:

614

ALSPAC

AF:

0.171

AC:

658

ESP6500AA

AF:

0.0311

AC:

137

ESP6500EA

AF:

0.165

AC:

1415

ExAC

AF:

0.132

AC:

15971

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

EpiCase

AF:

0.156

EpiControl

AF:

0.153

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inflammatory bowel disease 28

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
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	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 28, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

REVEL

Benign

0.048

Sift

Benign

0.12

Sift4G

Benign

0.11

Polyphen

0.75

Vest4

0.084

MPC

0.20

ClinPred

0.0043

GERP RS

2.0

Varity_R

0.24

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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