21-33268483-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000628.5(IL10RB):c.139A>G(p.Lys47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,124 control chromosomes in the GnomAD database, including 66,866 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 Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5821 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61045 hom. )

Consequence

IL10RB
NM_000628.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.677

Publications

117 publications found

Variant links:

Genes affected

IL10RB (HGNC:5965): (interleukin 10 receptor subunit beta) The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008]

IL10RB Gene-Disease associations (from GenCC):

inflammatory bowel disease 25
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
IL10-related early-onset inflammatory bowel disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IL10RB links:

IFNAR2-IL10RB (HGNC:):

IFNAR2-IL10RB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.5644255E-4).

BP6

Variant 21-33268483-A-G is Benign according to our data. Variant chr21-33268483-A-G is described in ClinVar as Benign. ClinVar VariationId is 16923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL10RB	NM_000628.5	MANE Select	c.139A>G	p.Lys47Glu	missense	Exon 2 of 7	NP_000619.3
IFNAR2-IL10RB	NM_001414505.1		c.799A>G	p.Lys267Glu	missense	Exon 8 of 13	NP_001401434.1	H0Y3Z8
IL10RB	NM_001405850.1		c.139A>G	p.Lys47Glu	missense	Exon 2 of 7	NP_001392779.1	A0A1B0GU52

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.139A>G	p.Lys47Glu	missense	Exon 2 of 7	ENSP00000290200.2	Q08334
IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.799A>G	p.Lys267Glu	missense	Exon 8 of 13	ENSP00000388223.3	H0Y3Z8
IL10RB	ENST00000896213.1		c.139A>G	p.Lys47Glu	missense	Exon 2 of 7	ENSP00000566272.1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38639

AN:

152118

Hom.:

5821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.253

GnomAD2 exomes

AF:

0.330

AC:

83064

AN:

251442

AF XY:

0.330

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.278

AC:

405506

AN:

1460888

Hom.:

61045

Cov.:

AF XY:

0.281

AC XY:

204127

AN XY:

726848

show subpopulations

African (AFR)

AF:

0.119

AC:

3985

AN:

33470

American (AMR)

AF:

0.491

AC:

21959

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7353

AN:

26128

East Asian (EAS)

AF:

0.555

AC:

22042

AN:

39684

South Asian (SAS)

AF:

0.381

AC:

32889

AN:

86238

European-Finnish (FIN)

AF:

0.320

AC:

17081

AN:

53418

Middle Eastern (MID)

AF:

0.340

AC:

1956

AN:

5750

European-Non Finnish (NFE)

AF:

0.253

AC:

280663

AN:

1111130

Other (OTH)

AF:

0.291

AC:

17578

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

15791

31581

47372

63162

78953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9722

19444

29166

38888

48610

<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:

0.254

AC:

38649

AN:

152236

Hom.:

5821

Cov.:

AF XY:

0.263

AC XY:

19580

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.126

AC:

5252

AN:

41562

American (AMR)

AF:

0.386

AC:

5899

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

984

AN:

3472

East Asian (EAS)

AF:

0.569

AC:

2951

AN:

5186

South Asian (SAS)

AF:

0.392

AC:

1892

AN:

4822

European-Finnish (FIN)

AF:

0.324

AC:

3430

AN:

10590

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17398

AN:

67996

Other (OTH)

AF:

0.255

AC:

539

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1421

2841

4262

5682

7103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.266

Hom.:

26542

Bravo

AF:

0.256

TwinsUK

AF:

0.253

AC:

939

ALSPAC

AF:

0.258

AC:

994

ESP6500AA

AF:

0.131

AC:

576

ESP6500EA

AF:

0.257

AC:

2214

ExAC

AF:

0.319

AC:

38727

Asia WGS

AF:

0.465

AC:

1615

AN:

3478

EpiCase

AF:

0.275

EpiControl

AF:

0.275

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Inflammatory bowel disease 25 (2)

not provided (1)

Hepatitis B virus, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.067

Eigen_PC

Benign

0.010

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.47

MetaRNN

Benign

0.00076

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

PhyloP100

0.68

PROVEAN

Benign

-1.9

REVEL

Benign

0.10

Sift

Benign

0.084

Sift4G

Benign

0.29

Polyphen

0.58

Vest4

0.043

MPC

0.50

ClinPred

0.015

GERP RS

2.6

Varity_R

0.39

gMVP

0.62

Mutation Taster

=80/20

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over