rs112317511

Positions:

chr11-117988450-A-G

Variant summary

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

The NM_001558.4(IL10RA):c.136A>G(p.Thr46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,614,068 control chromosomes in the GnomAD database, including 6 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 0.0026 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.362

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=0.007986456).

BP6

Variant 11-117988450-A-G is Benign according to our data. Variant chr11-117988450-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 470620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117988450-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00261 (398/152206) while in subpopulation AFR AF= 0.00867 (360/41510). AF 95% confidence interval is 0.00793. There are 5 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 32. 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	Protein
IL10RA	NM_001558.4 linkuse as main transcript	c.136A>G	p.Thr46Ala	missense_variant	2/7	ENST00000227752.8	NP_001549.2
IL10RA	XM_047426882.1 linkuse as main transcript	c.76A>G	p.Thr26Ala	missense_variant	2/7		XP_047282838.1
IL10RA	XM_047426884.1 linkuse as main transcript	c.-133A>G		5_prime_UTR_variant	1/5		XP_047282840.1
IL10RA	NR_026691.2 linkuse as main transcript	n.340A>G		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.136A>G	p.Thr46Ala	missense_variant	2/7	1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000851

AC:

214

AN:

251494

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00830

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000424

AC:

620

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

270

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00261

AC:

398

AN:

152206

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00867

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000816

Hom.:

Bravo

AF:

0.00283

ESP6500AA

AF:

0.00818

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00110

AC:

133

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	IL10RA: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
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 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.1

DANN

Benign

0.68

DEOGEN2

Benign

0.16

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.12

Sift

Benign

0.74

Sift4G

Benign

0.83

Polyphen

0.0030

Vest4

0.24

MVP

0.64

MPC

0.21

ClinPred

0.0034

GERP RS

4.0

Varity_R

0.20

gMVP

0.39

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