Variant rs6522 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002186.3(IL9R):c.715G>C(p.Glu239Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,204 control chromosomes in the GnomAD database, including 25 homozygotes. There are 742 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0061 ( 10 hom., 368 hem., cov: 32)

Exomes 𝑓: 0.00070 ( 15 hom. 374 hem. )

Consequence

IL9R
NM_002186.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0230

Variant links:

Genes affected

IL9R (HGNC:6030): (interleukin 9 receptor) The protein encoded by this gene is a cytokine receptor that specifically mediates the biological effects of interleukin 9 (IL9). The functional IL9 receptor complex requires this protein as well as the interleukin 2 receptor, gamma (IL2RG), a common gamma subunit shared by the receptors of many different cytokines. The ligand binding of this receptor leads to the activation of various JAK kinases and STAT proteins, which connect to different biologic responses. This gene is located at the pseudoautosomal regions of X and Y chromosomes. Genetic studies suggested an association of this gene with the development of asthma. Multiple pseudogenes on chromosome 9, 10, 16, and 18 have been described. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

IL9R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034928322).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0061 (929/152214) while in subpopulation AFR AF= 0.0215 (893/41534). AF 95% confidence interval is 0.0203. There are 10 homozygotes in gnomad4. There are 368 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL9R	NM_002186.3 linkuse as main transcript	c.715G>C	p.Glu239Gln	missense_variant	6/9	ENST00000244174.11	NP_002177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL9R	ENST00000244174.11 linkuse as main transcript	c.715G>C	p.Glu239Gln	missense_variant	6/9	1	NM_002186.3	ENSP00000244174	P1	Q01113-1
IL9R	ENST00000369423.7 linkuse as main transcript	c.820G>C	p.Glu274Gln	missense_variant	7/9	1		ENSP00000358431		Q01113-3

Frequencies

GnomAD3 genomes

AF:

0.00608

AC:

925

AN:

152096

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

366

AN XY:

74286

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00160

AC:

403

AN:

251142

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000699

AC:

1021

AN:

1460990

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

374

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00610

AC:

929

AN:

152214

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

368

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00475

Bravo

AF:

0.00666

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00193

AC:

234

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.2

DANN

Benign

0.97

DEOGEN2

Benign

0.045

T;.

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.019

Sift

Benign

0.13

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.11

B;.

MVP

0.27

MPC

0.0025

ClinPred

0.0026

GERP RS

0.32

Varity_R

0.081

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over