dbSNP rs748428395: IL10RA:p.Arg16Ser (chr11-117986513-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001558.4(IL10RA):c.46C>A(p.Arg16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL10RA
NM_001558.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

inflammatory bowel disease 28
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
IL10-related early-onset inflammatory bowel disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IL10RA links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07806128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001558.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	NM_001558.4	MANE Select	c.46C>A	p.Arg16Ser	missense	Exon 1 of 7	NP_001549.2	Q13651
	IL10RA	NR_026691.2		n.120C>A		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.46C>A	p.Arg16Ser	missense	Exon 1 of 7	ENSP00000227752.4	Q13651
IL10RA	ENST00000951964.1		c.46C>A	p.Arg16Ser	missense	Exon 1 of 7	ENSP00000622023.1
IL10RA	ENST00000885116.1		c.46C>A	p.Arg16Ser	missense	Exon 1 of 7	ENSP00000555175.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1403534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692822

African (AFR)

AF:

0.00

AC:

AN:

31736

American (AMR)

AF:

0.00

AC:

AN:

36582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25236

East Asian (EAS)

AF:

0.00

AC:

AN:

36072

South Asian (SAS)

AF:

0.00

AC:

AN:

79490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081542

Other (OTH)

AF:

0.00

AC:

AN:

58144

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000194

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.4

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.090

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.37

M_CAP

Benign

0.027

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

-1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.010

REVEL

Benign

0.052

Sift

Benign

0.50

Sift4G

Benign

0.53

Polyphen

0.010

Vest4

0.14

MutPred

0.49

Gain of loop (P = 0.0013)

MVP

0.60

MPC

0.24

ClinPred

0.041

GERP RS

-3.2

PromoterAI

-0.073

Neutral

(source)

Varity_R

0.079

gMVP

0.36

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over