Genetic Variant IL10RA:c.368-127T>C (chr11-117993114-T-C) – 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.368-127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 821,792 control chromosomes in the GnomAD database, including 138,644 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 0.51 ( 21463 hom., cov: 31)

Exomes 𝑓: 0.58 ( 117181 hom. )

Consequence

IL10RA
NM_001558.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

16 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: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4 link	c.368-127T>C		intron_variant	Intron 3 of 6	ENST00000227752.8	NP_001549.2	Q13651

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 link	c.368-127T>C		intron_variant	Intron 3 of 6	1	NM_001558.4	ENSP00000227752.4		Q13651

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77910

AN:

151922

Hom.:

21459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.920

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.551

GnomAD4 exome

AF:

0.583

AC:

390677

AN:

669752

Hom.:

117181

Cov.:

AF XY:

0.584

AC XY:

207861

AN XY:

355958

show subpopulations

African (AFR)

AF:

0.316

AC:

5571

AN:

17654

American (AMR)

AF:

0.657

AC:

24856

AN:

37854

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

12119

AN:

19838

East Asian (EAS)

AF:

0.909

AC:

30958

AN:

34044

South Asian (SAS)

AF:

0.613

AC:

40244

AN:

65616

European-Finnish (FIN)

AF:

0.497

AC:

23843

AN:

47952

Middle Eastern (MID)

AF:

0.573

AC:

2401

AN:

4188

European-Non Finnish (NFE)

AF:

0.565

AC:

230932

AN:

408660

Other (OTH)

AF:

0.582

AC:

19753

AN:

33946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

7977

15954

23931

31908

39885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2906

5812

8718

11624

14530

<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:

0.513

AC:

77930

AN:

152040

Hom.:

21463

Cov.:

AF XY:

0.516

AC XY:

38350

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.320

AC:

13272

AN:

41468

American (AMR)

AF:

0.603

AC:

9211

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2150

AN:

3472

East Asian (EAS)

AF:

0.921

AC:

4766

AN:

5176

South Asian (SAS)

AF:

0.622

AC:

2995

AN:

4816

European-Finnish (FIN)

AF:

0.487

AC:

5145

AN:

10558

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38498

AN:

67954

Other (OTH)

AF:

0.547

AC:

1155

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1770

3541

5311

7082

8852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.557

Hom.:

29489

Bravo

AF:

0.515

Asia WGS

AF:

0.706

AC:

2452

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.0

(source)

DANN

Benign

0.79

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over