chr21-33268483-A-G

Position:

chr21-33268483-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000290200.7(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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5821 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61045 hom. )

Consequence

IL10RB
ENST00000290200.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.677

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 links:

IFNAR2-IL10RB (HGNC:):

IFNAR2-IL10RB 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=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 id is 16923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-33268483-A-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RB	NM_000628.5 linkuse as main transcript	c.139A>G	p.Lys47Glu	missense_variant	2/7	ENST00000290200.7	NP_000619.3
IFNAR2-IL10RB	NM_001414505.1 linkuse as main transcript	c.799A>G	p.Lys267Glu	missense_variant	8/13		NP_001401434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7 linkuse as main transcript	c.139A>G	p.Lys47Glu	missense_variant	2/7	1	NM_000628.5	ENSP00000290200	P2

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

GnomAD3 exomes

AF:

0.330

AC:

83064

AN:

251442

Hom.:

15733

AF XY:

0.330

AC XY:

44818

AN XY:

135904

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 SAS exome

AF:

0.385

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

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.555

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.254

AC:

38649

AN:

152236

Hom.:

5821

Cov.:

AF XY:

0.263

AC XY:

19580

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.392

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.271

Hom.:

15065

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

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 75% of patients studied by a panel of primary immunodeficiencies. Number of patients: 72. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, associated with susceptibility to hepatitis -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Inflammatory bowel disease 25

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hepatitis B virus, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 13, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.30

CADD

Benign

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

MutationTaster

Benign

1.0

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

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