Genetic Variant IL10RB:c.805-1934T>G (chr21-33294250-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000628.5(IL10RB):c.805-1934T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 329,250 control chromosomes in the GnomAD database, including 944 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 0.063 ( 375 hom., cov: 31)

Exomes 𝑓: 0.070 ( 569 hom. )

Consequence

IL10RB
NM_000628.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

13 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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5 link	c.805-1934T>G		intron_variant	Intron 6 of 6	ENST00000290200.7	NP_000619.3	Q08334

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7 link	c.805-1934T>G		intron_variant	Intron 6 of 6	1	NM_000628.5	ENSP00000290200.2		Q08334
IFNAR2-IL10RB	ENST00000433395.7 link	c.1465-1934T>G		intron_variant	Intron 12 of 12	5		ENSP00000388223.3		H0Y3Z8

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9525

AN:

152024

Hom.:

373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0754

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0781

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0584

Gnomad OTH

AF:

0.0589

GnomAD4 exome

AF:

0.0696

AC:

12333

AN:

177108

Hom.:

569

AF XY:

0.0764

AC XY:

7454

AN XY:

97564

show subpopulations

African (AFR)

AF:

0.0777

AC:

355

AN:

4568

American (AMR)

AF:

0.0263

AC:

250

AN:

9490

Ashkenazi Jewish (ASJ)

AF:

0.0612

AC:

239

AN:

3906

East Asian (EAS)

AF:

0.000861

AC:

AN:

6970

South Asian (SAS)

AF:

0.126

AC:

4659

AN:

37012

European-Finnish (FIN)

AF:

0.0742

AC:

599

AN:

8068

Middle Eastern (MID)

AF:

0.0690

AC:

AN:

594

European-Non Finnish (NFE)

AF:

0.0576

AC:

5645

AN:

97932

Other (OTH)

AF:

0.0629

AC:

539

AN:

8568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

510

1020

1529

2039

2549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0626

AC:

9521

AN:

152142

Hom.:

375

Cov.:

AF XY:

0.0638

AC XY:

4749

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0752

AC:

3121

AN:

41494

American (AMR)

AF:

0.0377

AC:

576

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

191

AN:

3470

East Asian (EAS)

AF:

0.000966

AC:

AN:

5176

South Asian (SAS)

AF:

0.134

AC:

644

AN:

4822

European-Finnish (FIN)

AF:

0.0781

AC:

826

AN:

10582

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0584

AC:

3969

AN:

67992

Other (OTH)

AF:

0.0583

AC:

123

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

444

888

1331

1775

2219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0587

Hom.:

649

Bravo

AF:

0.0580

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.7

(source)

DANN

Benign

0.33

PhyloP100

-0.030

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