rs4252303

Positions:

chr11-117989590-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001558.4(IL10RA):c.337G>A(p.Val113Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,614,108 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 93 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.16

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=0.004027009).

BP6

Variant 11-117989590-G-A is Benign according to our data. Variant chr11-117989590-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 302544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117989590-G-A is described in Lovd as [Benign]. Variant chr11-117989590-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00628 (957/152282) while in subpopulation AMR AF= 0.0098 (150/15302). AF 95% confidence interval is 0.00902. There are 5 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL10RA	NM_001558.4 linkuse as main transcript	c.337G>A	p.Val113Ile	missense_variant	3/7	ENST00000227752.8
IL10RA	XM_047426882.1 linkuse as main transcript	c.277G>A	p.Val93Ile	missense_variant	3/7
IL10RA	XM_047426884.1 linkuse as main transcript	c.-81+1088G>A		intron_variant
IL10RA	NR_026691.2 linkuse as main transcript	n.541G>A		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.337G>A	p.Val113Ile	missense_variant	3/7	1	NM_001558.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

957

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00963

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00680

AC:

1709

AN:

251400

Hom.:

AF XY:

0.00652

AC XY:

886

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00908

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.00956

AC:

13982

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

6827

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00885

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00470

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00798

GnomAD4 genome

AF:

0.00628

AC:

957

AN:

152282

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00963

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00855

Hom.:

Bravo

AF:

0.00660

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00364

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00701

AC:

851

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inflammatory bowel disease 28

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 17, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	Invitae	Jan 29, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

IL10RA: BP4, BS1, BS2 -

IL10RA-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.0010

DANN

Benign

0.66

DEOGEN2

Benign

0.096

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.051

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.14

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.17

REVEL

Benign

0.14

Sift

Benign

0.40

Sift4G

Benign

0.55

Polyphen

0.0030

Vest4

0.066

MVP

0.29

MPC

0.17

ClinPred

0.0097

GERP RS

-9.9

Varity_R

0.12

gMVP

0.18

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

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