11-117994131-A-G

Position:

chr11-117994131-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.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. 14/20 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

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=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 id is 302548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117994131-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
IL10RA	NM_001558.4 linkuse as main transcript	c.670A>G	p.Ile224Val	missense_variant	5/7	ENST00000227752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.670A>G	p.Ile224Val	missense_variant	5/7	1	NM_001558.4	P1

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

GnomAD3 exomes

AF:

0.0821

AC:

20641

AN:

251262

Hom.:

1585

AF XY:

0.0820

AC XY:

11142

AN XY:

135830

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 SAS exome

AF:

0.105

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

Gnomad4 AFR exome

AF:

0.00875

Gnomad4 AMR exome

AF:

0.0725

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.373

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0577

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.0742

GnomAD4 genome

AF:

0.0544

AC:

8275

AN:

152212

Hom.:

499

Cov.:

AF XY:

0.0575

AC XY:

4277

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0530

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0603

Gnomad4 NFE

AF:

0.0529

Gnomad4 OTH

AF:

0.0522

Alfa

AF:

0.0599

Hom.:

816

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29248579, 29755507) -

Inflammatory bowel disease 28

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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

0.071

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0020

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

MutationTaster

Benign

1.0

P;P;P

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

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

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