rs150140303

Positions:

chr11-117988389-G-T

Variant summary

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

The NM_001558.4(IL10RA):c.75G>T(p.Glu25Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,614,174 control chromosomes in the GnomAD database, including 4 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 (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 3 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.678

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=0.0065312088).

BP6

Variant 11-117988389-G-T is Benign according to our data. Variant chr11-117988389-G-T is described in ClinVar as [Benign]. Clinvar id is 538059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117988389-G-T is described in Lovd as [Likely_benign]. Variant chr11-117988389-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00299 (455/152326) while in subpopulation AFR AF= 0.0102 (424/41568). AF 95% confidence interval is 0.0094. There are 1 homozygotes in gnomad4. There are 219 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL10RA	NM_001558.4 linkuse as main transcript	c.75G>T	p.Glu25Asp	missense_variant	2/7	ENST00000227752.8	NP_001549.2
IL10RA	XM_047426882.1 linkuse as main transcript	c.15G>T	p.Glu5Asp	missense_variant	2/7		XP_047282838.1
IL10RA	NR_026691.2 linkuse as main transcript	n.279G>T		non_coding_transcript_exon_variant	3/8
IL10RA	XM_047426884.1 linkuse as main transcript			upstream_gene_variant			XP_047282840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.75G>T	p.Glu25Asp	missense_variant	2/7	1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

456

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000835

AC:

210

AN:

251448

Hom.:

AF XY:

0.000603

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000298

AC:

436

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

184

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00977

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.00299

AC:

455

AN:

152326

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000705

Hom.:

Bravo

AF:

0.00361

ESP6500AA

AF:

0.0139

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00105

AC:

127

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inflammatory bowel disease 28

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
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. -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.1

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.50

D;D;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

REVEL

Benign

0.097

Sift

Benign

0.11

Sift4G

Benign

0.37

Polyphen

0.0070

Vest4

0.14

MutPred

0.59

Loss of glycosylation at P30 (P = 0.1509);

MVP

0.68

MPC

0.19

ClinPred

0.00052

GERP RS

-2.5

Varity_R

0.31

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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