Genetic Variant IL10RB:c.804+9006G>A (chr21-33297267-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001405850.1(IL10RB):c.804+9006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,972 control chromosomes in the GnomAD database, including 2,365 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 0.16 ( 2365 hom., cov: 30)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

IL10RB
NM_001405850.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

12 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:

ENSG00000294417 (HGNC:):

ENSG00000294417 links:

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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 (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405850.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
IL10RB	NM_001405850.1	c.804+9006G>A	intron	N/A	NP_001392779.1
IL10RB	NM_001405849.1	c.804+9006G>A	intron	N/A	NP_001392778.1
IL10RB	NR_175973.1	n.745+9006G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL10RB	ENST00000609556.3	TSL:5	c.804+9006G>A	intron	N/A	ENSP00000489965.2
IL10RB	ENST00000637650.2	TSL:5	c.804+9006G>A	intron	N/A	ENSP00000489716.2
ENSG00000294417	ENST00000723465.1		n.396+1585C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23635

AN:

151778

Hom.:

2371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.154

GnomAD4 exome

AF:

0.145

AC:

AN:

Hom.:

Cov.:

AF XY:

0.111

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.153

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.155

AC:

23619

AN:

151896

Hom.:

2365

Cov.:

AF XY:

0.160

AC XY:

11904

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0388

AC:

1608

AN:

41474

American (AMR)

AF:

0.163

AC:

2483

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

428

AN:

3464

East Asian (EAS)

AF:

0.360

AC:

1857

AN:

5164

South Asian (SAS)

AF:

0.240

AC:

1156

AN:

4810

European-Finnish (FIN)

AF:

0.253

AC:

2661

AN:

10508

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12877

AN:

67940

Other (OTH)

AF:

0.152

AC:

320

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

969

1938

2907

3876

4845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.133

Hom.:

398

Bravo

AF:

0.145

Asia WGS

AF:

0.323

AC:

1121

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

7.8

(source)

DANN

Benign

0.55

PhyloP100

1.2

Mutation Taster

=99/1

polymorphism

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over