11-117994131-A-G

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.670A>G(p.Ile224Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 1,613,634 control chromosomes in the GnomAD database, including 6,059 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I224F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.054 ( 499 hom., cov: 32)

Exomes 𝑓: 0.065 ( 5560 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.04

Publications

37 publications found

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 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=5.786419E-4).

BP6

Variant 11-117994131-A-G is Benign according to our data. Variant chr11-117994131-A-G is described in ClinVar as Benign. ClinVar VariationId is 302548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
IL10RA	NM_001558.4 link	c.670A>G	p.Ile224Val	missense_variant	Exon 5 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.670A>G	p.Ile224Val	missense_variant	Exon 5 of 7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8276

AN:

152094

Hom.:

499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0529

Gnomad OTH

AF:

0.0513

GnomAD2 exomes

AF:

0.0821

AC:

20641

AN:

251262

AF XY:

0.0820

show subpopulations

Gnomad AFR exome

AF:

0.00984

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.0517

Gnomad OTH exome

AF:

0.0701

GnomAD4 exome

AF:

0.0648

AC:

94761

AN:

1461422

Hom.:

5560

Cov.:

AF XY:

0.0661

AC XY:

48087

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.00875

AC:

293

AN:

33478

American (AMR)

AF:

0.0725

AC:

3243

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

2802

AN:

26128

East Asian (EAS)

AF:

0.373

AC:

14805

AN:

39680

South Asian (SAS)

AF:

0.104

AC:

8968

AN:

86242

European-Finnish (FIN)

AF:

0.0577

AC:

3081

AN:

53406

Middle Eastern (MID)

AF:

0.0432

AC:

248

AN:

5738

European-Non Finnish (NFE)

AF:

0.0511

AC:

56840

AN:

1111652

Other (OTH)

AF:

0.0742

AC:

4481

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

3961

7922

11884

15845

19806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2306

4612

6918

9224

11530

<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:

0.0544

AC:

8275

AN:

152212

Hom.:

499

Cov.:

AF XY:

0.0575

AC XY:

4277

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0107

AC:

443

AN:

41544

American (AMR)

AF:

0.0530

AC:

811

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

366

AN:

3468

East Asian (EAS)

AF:

0.339

AC:

1752

AN:

5174

South Asian (SAS)

AF:

0.107

AC:

516

AN:

4818

European-Finnish (FIN)

AF:

0.0603

AC:

639

AN:

10604

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0529

AC:

3595

AN:

67992

Other (OTH)

AF:

0.0522

AC:

110

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

379

758

1137

1516

1895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0586

Hom.:

1179

Bravo

AF:

0.0518

TwinsUK

AF:

0.0510

AC:

189

ALSPAC

AF:

0.0506

AC:

195

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0559

AC:

480

ExAC

AF:

0.0807

AC:

9795

Asia WGS

AF:

0.197

AC:

685

AN:

3478

EpiCase

AF:

0.0535

EpiControl

AF:

0.0560

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29248579, 29755507) -

Inflammatory bowel disease 28

Benign:2

Jan 13, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0020

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.095

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.31

MetaRNN

Benign

0.00058

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

-2.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.17

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.010

MPC

0.18

ClinPred

0.00065

GERP RS

-3.9

Varity_R

0.13

gMVP

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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