11-117986488-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001558.4(IL10RA):c.21G>C(p.Val7Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0078 in 1,556,200 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 50 hom. )

Consequence

IL10RA
NM_001558.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.40

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-117986488-G-C is Benign according to our data. Variant chr11-117986488-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 281990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117986488-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.4 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0055 (838/152330) while in subpopulation NFE AF= 0.00925 (629/68004). AF 95% confidence interval is 0.00865. There are 3 homozygotes in gnomad4. There are 383 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4 link	c.21G>C	p.Val7Val	synonymous_variant	Exon 1 of 7	ENST00000227752.8	NP_001549.2	Q13651
IL10RA	XM_047426882.1 link	c.-319G>C		5_prime_UTR_variant	Exon 1 of 7		XP_047282838.1
IL10RA	NR_026691.2 link	n.95G>C		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 link	c.21G>C	p.Val7Val	synonymous_variant	Exon 1 of 7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

839

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00490

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00925

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00466

AC:

737

AN:

158048

Hom.:

AF XY:

0.00469

AC XY:

395

AN XY:

84174

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000945

Gnomad EAS exome

AF:

0.0000848

Gnomad SAS exome

AF:

0.000347

Gnomad FIN exome

AF:

0.00404

Gnomad NFE exome

AF:

0.00879

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00805

AC:

11302

AN:

1403870

Hom.:

Cov.:

AF XY:

0.00767

AC XY:

5315

AN XY:

693046

show subpopulations

Gnomad4 AFR exome

AF:

0.00145

Gnomad4 AMR exome

AF:

0.00316

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.0000554

Gnomad4 SAS exome

AF:

0.000377

Gnomad4 FIN exome

AF:

0.00408

Gnomad4 NFE exome

AF:

0.00974

Gnomad4 OTH exome

AF:

0.00590

GnomAD4 genome

AF:

0.00550

AC:

838

AN:

152330

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

383

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.00925

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00680

Hom.:

Bravo

AF:

0.00529

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IL10RA: BP4, BP7, BS2 -

Inflammatory bowel disease 28

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not specified

Benign:1

Aug 10, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.57

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