rs2229114

Positions:

chr11-117999163-C-T

Variant summary

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

The ENST00000227752.8(IL10RA):c.1259C>T(p.Ser420Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,614,092 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S420S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.032 ( 116 hom., cov: 33)

Exomes 𝑓: 0.041 ( 1431 hom. )

Consequence

IL10RA
ENST00000227752.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.738

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=0.0020552278).

BP6

Variant 11-117999163-C-T is Benign according to our data. Variant chr11-117999163-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 302556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117999163-C-T is described in Lovd as [Benign]. Variant chr11-117999163-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0321 (4888/152330) while in subpopulation NFE AF= 0.0484 (3291/68036). AF 95% confidence interval is 0.047. There are 116 homozygotes in gnomad4. There are 2386 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 116 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4 linkuse as main transcript	c.1259C>T	p.Ser420Leu	missense_variant	7/7	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.1259C>T	p.Ser420Leu	missense_variant	7/7	1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4888

AN:

152212

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00815

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0478

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0321

AC:

8051

AN:

251132

Hom.:

176

AF XY:

0.0318

AC XY:

4323

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.00727

Gnomad AMR exome

AF:

0.0303

Gnomad ASJ exome

AF:

0.0461

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00673

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0494

Gnomad OTH exome

AF:

0.0413

GnomAD4 exome

AF:

0.0413

AC:

60410

AN:

1461762

Hom.:

1431

Cov.:

AF XY:

0.0407

AC XY:

29604

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00741

Gnomad4 AMR exome

AF:

0.0311

Gnomad4 ASJ exome

AF:

0.0461

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00670

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0481

Gnomad4 OTH exome

AF:

0.0380

GnomAD4 genome

AF:

0.0321

AC:

4888

AN:

152330

Hom.:

116

Cov.:

AF XY:

0.0320

AC XY:

2386

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00813

Gnomad4 AMR

AF:

0.0478

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0157

Gnomad4 NFE

AF:

0.0484

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0471

Hom.:

194

Bravo

AF:

0.0330

TwinsUK

AF:

0.0442

AC:

164

ALSPAC

AF:

0.0444

AC:

171

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.0491

AC:

422

ExAC

AF:

0.0318

AC:

3865

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0510

EpiControl

AF:

0.0521

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	See Variant Classification Assertion Criteria. -

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	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

REVEL

Benign

0.049

Sift

Benign

0.072

Sift4G

Uncertain

0.0070

Polyphen

0.32

Vest4

0.026

MPC

0.20

ClinPred

0.0077

GERP RS

1.8

Varity_R

0.042

gMVP

0.19

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