Genetic Variant IL10RB:c.173+3260G>T (chr21-33271777-G-T) – 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.173+3260G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,740 control chromosomes in the GnomAD database, including 4,417 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 0.23 ( 4417 hom., cov: 31)

Consequence

IL10RB
NM_000628.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.936

Publications

17 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

new If you want to explore the variant's impact on the transcript NM_000628.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 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	Effect	Exon Rank	Protein	UniProt
IL10RB	NM_000628.5	MANE Select	c.173+3260G>T	intron	N/A	NP_000619.3
IFNAR2-IL10RB	NM_001414505.1		c.833+3260G>T	intron	N/A	NP_001401434.1	H0Y3Z8
IL10RB	NM_001405850.1		c.173+3260G>T	intron	N/A	NP_001392779.1	A0A1B0GU52

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.173+3260G>T	intron	N/A	ENSP00000290200.2	Q08334
IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.833+3260G>T	intron	N/A	ENSP00000388223.3	H0Y3Z8
IL10RB	ENST00000896213.1		c.173+3260G>T	intron	N/A	ENSP00000566272.1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34768

AN:

151624

Hom.:

4415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.229

AC:

34782

AN:

151740

Hom.:

4417

Cov.:

AF XY:

0.236

AC XY:

17472

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.173

AC:

7144

AN:

41326

American (AMR)

AF:

0.293

AC:

4470

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

839

AN:

3464

East Asian (EAS)

AF:

0.541

AC:

2789

AN:

5158

South Asian (SAS)

AF:

0.319

AC:

1532

AN:

4810

European-Finnish (FIN)

AF:

0.278

AC:

2920

AN:

10498

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.211

AC:

14312

AN:

67924

Other (OTH)

AF:

0.228

AC:

479

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1337

2674

4012

5349

6686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.223

Hom.:

11505

Bravo

AF:

0.233

Asia WGS

AF:

0.443

AC:

1538

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.8

(source)

DANN

Benign

0.63

PhyloP100

0.94

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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