rs3135932

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S159S) has been classified as Likely 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

Publications

61 publications found

Variant links:

COSMIC-nc: COSV107188502

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

IL10RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 197197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
IL10RA	NM_001558.4 link	c.475A>G	p.Ser159Gly	missense_variant	Exon 4 of 7	ENST00000227752.8	NP_001549.2	Q13651

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 link	c.475A>G	p.Ser159Gly	missense_variant	Exon 4 of 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

GnomAD2 exomes

AF:

0.130

AC:

32588

AN:

251430

AF XY:

0.136

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 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

African (AFR)

AF:

0.0220

AC:

735

AN:

33478

American (AMR)

AF:

0.0550

AC:

2461

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3367

AN:

26136

East Asian (EAS)

AF:

0.000806

AC:

AN:

39678

South Asian (SAS)

AF:

0.162

AC:

13937

AN:

86246

European-Finnish (FIN)

AF:

0.203

AC:

10859

AN:

53414

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5768

European-Non Finnish (NFE)

AF:

0.166

AC:

184612

AN:

1111588

Other (OTH)

AF:

0.142

AC:

8586

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

10577

21153

31730

42306

52883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6272

12544

18816

25088

31360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.114

AC:

17399

AN:

152294

Hom.:

1413

Cov.:

AF XY:

0.115

AC XY:

8546

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0285

AC:

1187

AN:

41578

American (AMR)

AF:

0.0728

AC:

1113

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

460

AN:

3468

East Asian (EAS)

AF:

0.00404

AC:

AN:

5194

South Asian (SAS)

AF:

0.158

AC:

761

AN:

4830

European-Finnish (FIN)

AF:

0.199

AC:

2106

AN:

10594

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11414

AN:

68012

Other (OTH)

AF:

0.102

AC:

216

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

770

1540

2309

3079

3849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.147

Hom.:

7407

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 28, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

0.41

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

Mutation Taster

=80/20

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over