rs4252249

Positions:

chr11-117988494-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001558.4(IL10RA):c.180G>A(p.Ala60Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,030 control chromosomes in the GnomAD database, including 10,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1261 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9155 hom. )

Consequence

IL10RA
NM_001558.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.816

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:

IL10RA (HGNC:):

IL10RA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-117988494-G-A is Benign according to our data. Variant chr11-117988494-G-A is described in ClinVar as [Benign]. Clinvar id is 302538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117988494-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.816 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4 linkuse as main transcript	c.180G>A	p.Ala60Ala	synonymous_variant	2/7	ENST00000227752.8	NP_001549.2	Q13651
IL10RA	XM_047426882.1 linkuse as main transcript	c.120G>A	p.Ala40Ala	synonymous_variant	2/7		XP_047282838.1
IL10RA	XM_047426884.1 linkuse as main transcript	c.-89G>A		5_prime_UTR_variant	1/5		XP_047282840.1
IL10RA	NR_026691.2 linkuse as main transcript	n.384G>A		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.180G>A	p.Ala60Ala	synonymous_variant	2/7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18825

AN:

151962

Hom.:

1252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.115

AC:

28935

AN:

251442

Hom.:

1879

AF XY:

0.112

AC XY:

15247

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.0807

Gnomad EAS exome

AF:

0.0507

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.110

AC:

160273

AN:

1460950

Hom.:

9155

Cov.:

AF XY:

0.109

AC XY:

78926

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.0844

Gnomad4 EAS exome

AF:

0.0647

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.124

AC:

18860

AN:

152080

Hom.:

1261

Cov.:

AF XY:

0.123

AC XY:

9146

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.0726

Gnomad4 EAS

AF:

0.0562

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.109

Hom.:

1270

Bravo

AF:

0.129

Asia WGS

AF:

0.0820

AC:

287

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inflammatory bowel disease 28

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 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, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.8

DANN

Benign

0.68

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