rs4252250

Positions:

chr11-117988495-C-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.181C>G(p.Leu61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,614,046 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 44 hom. )

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.137

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027538538).

BP6

Variant 11-117988495-C-G is Benign according to our data. Variant chr11-117988495-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 302539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1924/152228) while in subpopulation AFR AF= 0.0432 (1793/41518). AF 95% confidence interval is 0.0415. There are 35 homozygotes in gnomad4. There are 919 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4 linkuse as main transcript	c.181C>G	p.Leu61Val	missense_variant	2/7	ENST00000227752.8	NP_001549.2	Q13651
IL10RA	XM_047426882.1 linkuse as main transcript	c.121C>G	p.Leu41Val	missense_variant	2/7		XP_047282838.1
IL10RA	XM_047426884.1 linkuse as main transcript	c.-88C>G		5_prime_UTR_variant	1/5		XP_047282840.1
IL10RA	NR_026691.2 linkuse as main transcript	n.385C>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.181C>G	p.Leu61Val	missense_variant	2/7	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1914

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00337

AC:

848

AN:

251474

Hom.:

AF XY:

0.00257

AC XY:

349

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0451

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00126

AC:

1843

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

826

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0440

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.0126

AC:

1924

AN:

152228

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

919

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.0151

ESP6500AA

AF:

0.0411

AC:

181

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00395

AC:

480

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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	Jan 30, 2024	- -
Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.6

DANN

Benign

0.89

DEOGEN2

Benign

0.13

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.91

REVEL

Benign

0.074

Sift

Benign

0.15

Sift4G

Benign

0.23

Polyphen

0.15

Vest4

0.18

MVP

0.64

MPC

0.24

ClinPred

0.0045

GERP RS

3.0

Varity_R

0.31

gMVP

0.49

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