rs2256111

Positions:

Variant summary

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

The NM_001558.4(IL10RA):c.459A>G(p.Ala153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,613,002 control chromosomes in the GnomAD database, including 217,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19804 hom., cov: 32)

Exomes 𝑓: 0.52 ( 197547 hom. )

Consequence

IL10RA
NM_001558.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.00400

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=-0.83).

BP6

Variant 11-117993332-A-G is Benign according to our data. Variant chr11-117993332-A-G is described in ClinVar as [Benign]. Clinvar id is 302546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117993332-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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.459A>G	p.Ala153=	synonymous_variant	4/7	ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.459A>G	p.Ala153=	synonymous_variant	4/7	1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

77087

AN:

152008

Hom.:

19784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.543

GnomAD3 exomes

AF:

0.533

AC:

133968

AN:

251408

Hom.:

36072

AF XY:

0.530

AC XY:

72051

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.615

Gnomad SAS exome

AF:

0.530

Gnomad FIN exome

AF:

0.443

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.518

AC:

757086

AN:

1460876

Hom.:

197547

Cov.:

AF XY:

0.518

AC XY:

376478

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.616

Gnomad4 ASJ exome

AF:

0.567

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.525

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.507

AC:

77144

AN:

152126

Hom.:

19804

Cov.:

AF XY:

0.507

AC XY:

37730

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.459

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.575

Gnomad4 EAS

AF:

0.600

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.523

Hom.:

41435

Bravo

AF:

0.517

Asia WGS

AF:

0.577

AC:

2004

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.523

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 77. Only high quality variants are reported. -

Inflammatory bowel disease 28

Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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