rs112317511

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001558.4(IL10RA):c.136A>G(p.Thr46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,614,068 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T46T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0026 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.362

Publications

4 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=0.007986456).

BP6

Variant 11-117988450-A-G is Benign according to our data. Variant chr11-117988450-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 470620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00261 (398/152206) while in subpopulation AFR AF = 0.00867 (360/41510). AF 95% confidence interval is 0.00793. There are 5 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4 link	c.136A>G	p.Thr46Ala	missense_variant	Exon 2 of 7	ENST00000227752.8	NP_001549.2	Q13651
IL10RA	XM_047426882.1 link	c.76A>G	p.Thr26Ala	missense_variant	Exon 2 of 7		XP_047282838.1
IL10RA	NR_026691.2 link	n.340A>G		non_coding_transcript_exon_variant	Exon 3 of 8
IL10RA	XM_047426884.1 link	c.-133A>G		5_prime_UTR_variant	Exon 1 of 5		XP_047282840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 link	c.136A>G	p.Thr46Ala	missense_variant	Exon 2 of 7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000851

AC:

214

AN:

251494

AF XY:

0.000633

show subpopulations

Gnomad AFR exome

AF:

0.00830

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000424

AC:

620

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

270

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00914

AC:

306

AN:

33476

American (AMR)

AF:

0.000402

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00429

AC:

112

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000102

AC:

113

AN:

1111984

Other (OTH)

AF:

0.000911

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00261

AC:

398

AN:

152206

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00867

AC:

360

AN:

41510

American (AMR)

AF:

0.000719

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68002

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.00283

ESP6500AA

AF:

0.00818

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00110

AC:

133

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL10RA: BP4, BS2 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Inflammatory bowel disease 28

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.1

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.16

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

PhyloP100

0.36

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.12

Sift

Benign

0.74

Sift4G

Benign

0.83

Polyphen

0.0030

Vest4

0.24

MVP

0.64

MPC

0.21

ClinPred

0.0034

GERP RS

4.0

Varity_R

0.20

gMVP

0.39

Mutation Taster

=297/3

polymorphism

(source)

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

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rs112317511

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