dbSNP rs1165667595: IL10RB:p.Ala2Gly (chr21-33266470-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000628.5(IL10RB):c.5C>G(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL10RB
NM_000628.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16335008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5 link	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 7	ENST00000290200.7	NP_000619.3	Q08334

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7 link	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 7	1	NM_000628.5	ENSP00000290200.2		Q08334
IFNAR2-IL10RB	ENST00000433395.7 link	c.710-1924C>G		intron_variant	Intron 7 of 12	5		ENSP00000388223.3		H0Y3Z8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389896

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

685982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31544

American (AMR)

AF:

0.00

AC:

AN:

35738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35798

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078904

Other (OTH)

AF:

0.00

AC:

AN:

57788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

PhyloP100

0.022

PROVEAN

Benign

-1.4

REVEL

Benign

0.059

Sift

Benign

0.037

Sift4G

Benign

0.26

Polyphen

0.026

Vest4

0.13

MutPred

0.27

Gain of disorder (P = 0.0694);

MVP

0.44

MPC

0.32

ClinPred

0.16

GERP RS

1.8

PromoterAI

-0.49

Neutral

(source)

Varity_R

0.057

gMVP

0.47

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over