Genetic Variant NM_000628.5:c.35G>A (chr21-33266500-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000628.5(IL10RB):c.35G>A(p.Cys12Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,390,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

IL10RB
NM_000628.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Publications

0 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 links:

IFNAR2-IL10RB (HGNC:):

IFNAR2-IL10RB links:

IL10RB-DT (HGNC:44303): (IL10RB divergent transcript)

IL10RB-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.35G>A	p.Cys12Tyr	missense	Exon 1 of 7	NP_000619.3
IL10RB	NM_001405850.1		c.35G>A	p.Cys12Tyr	missense	Exon 1 of 7	NP_001392779.1	A0A1B0GU52
IL10RB	NM_001405849.1		c.35G>A	p.Cys12Tyr	missense	Exon 1 of 7	NP_001392778.1	A0A1B0GTI5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.35G>A	p.Cys12Tyr	missense	Exon 1 of 7	ENSP00000290200.2	Q08334
IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.710-1894G>A		intron	N/A	ENSP00000388223.3	H0Y3Z8
IL10RB	ENST00000896213.1		c.35G>A	p.Cys12Tyr	missense	Exon 1 of 7	ENSP00000566272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1390586

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686402

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31612

American (AMR)

AF:

0.00

AC:

AN:

35832

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35928

South Asian (SAS)

AF:

0.00

AC:

AN:

79240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4502

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1079374

Other (OTH)

AF:

0.00

AC:

AN:

57862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inflammatory bowel disease 25 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.14

Eigen_PC

Benign

0.089

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.61

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

PhyloP100

1.3

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.17

Sift

Benign

0.057

Sift4G

Benign

0.077

Polyphen

0.73

Vest4

0.49

MutPred

0.71

Loss of catalytic residue at L13 (P = 0.0309)

MVP

0.79

MPC

0.55

ClinPred

0.94

GERP RS

2.8

PromoterAI

-0.083

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.69

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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