Genetic Variant IL10RA:c.-185C>T (chr11-117986283-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001558.4(IL10RA):c.-185C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 594,320 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.038 ( 275 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 96 hom. )

Consequence

IL10RA
NM_001558.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

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.-185C>T		upstream_gene	N/A	NP_001549.2	Q13651
	IL10RA	NR_026691.2		n.-111C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.-185C>T	upstream_gene	N/A	ENSP00000227752.4	Q13651
IL10RA	ENST00000951964.1		c.-185C>T	upstream_gene	N/A	ENSP00000622023.1
IL10RA	ENST00000885116.1		c.-185C>T	upstream_gene	N/A	ENSP00000555175.1

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5807

AN:

152146

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0273

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.0368

GnomAD4 exome

AF:

0.00924

AC:

4086

AN:

442058

Hom.:

AF XY:

0.00918

AC XY:

2157

AN XY:

234852

show subpopulations

African (AFR)

AF:

0.107

AC:

939

AN:

8770

American (AMR)

AF:

0.0281

AC:

409

AN:

14546

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

215

AN:

12530

East Asian (EAS)

AF:

0.0203

AC:

558

AN:

27542

South Asian (SAS)

AF:

0.0161

AC:

698

AN:

43288

European-Finnish (FIN)

AF:

0.0117

AC:

344

AN:

29492

Middle Eastern (MID)

AF:

0.0184

AC:

AN:

1900

European-Non Finnish (NFE)

AF:

0.00155

AC:

431

AN:

278946

Other (OTH)

AF:

0.0182

AC:

457

AN:

25044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

185

371

556

742

927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0382

AC:

5817

AN:

152262

Hom.:

275

Cov.:

AF XY:

0.0380

AC XY:

2825

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.116

AC:

4813

AN:

41550

American (AMR)

AF:

0.0272

AC:

416

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

AN:

3472

East Asian (EAS)

AF:

0.0180

AC:

AN:

5158

South Asian (SAS)

AF:

0.0188

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0102

AC:

108

AN:

10608

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00198

AC:

135

AN:

68014

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

267

533

800

1066

1333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00621

Hom.:

Bravo

AF:

0.0430

Asia WGS

AF:

0.0660

AC:

229

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.083

(source)

DANN

Benign

0.72

PhyloP100

-2.0

PromoterAI

0.022

Neutral

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over