NM_002186.3:c.991G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002186.3(IL9R):c.991G>A(p.Gly331Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,283,524 control chromosomes in the GnomAD database, including 2,010 homozygotes. There are 8,866 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 555 hom., 1345 hem., cov: 18)

Exomes 𝑓: 0.012 ( 1455 hom. 7521 hem. )

Consequence

IL9R
NM_002186.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.349

Publications

0 publications found

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:

ENSG00000270726 (HGNC:):

ENSG00000270726 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020613968).

BP6

Variant X-156009834-G-A is Benign according to our data. Variant chrX-156009834-G-A is described in ClinVar as [Benign]. Clinvar id is 769193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL9R	NM_002186.3 link	c.991G>A	p.Gly331Arg	missense_variant	Exon 9 of 9	ENST00000244174.11	NP_002177.2	Q01113-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL9R	ENST00000244174.11 link	c.991G>A	p.Gly331Arg	missense_variant	Exon 9 of 9	1	NM_002186.3	ENSP00000244174.5	Q01113-1
IL9R	ENST00000369423.8 link	c.1011G>A	p.Thr337Thr	synonymous_variant	Exon 9 of 9	1		ENSP00000358431.2	Q01113-3
ENSG00000270726	ENST00000483543.7 link	n.433+2227G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

2896

AN:

89966

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00601

Gnomad AMR

AF:

0.0165

Gnomad ASJ

AF:

0.00858

Gnomad EAS

AF:

0.0163

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.00870

Gnomad NFE

AF:

0.00928

Gnomad OTH

AF:

0.0233

GnomAD2 exomes

AF:

0.00702

AC:

1479

AN:

210536

AF XY:

0.00561

show subpopulations

Gnomad AFR exome

AF:

0.0725

Gnomad AMR exome

AF:

0.00550

Gnomad ASJ exome

AF:

0.00215

Gnomad EAS exome

AF:

0.00878

Gnomad FIN exome

AF:

0.00417

Gnomad NFE exome

AF:

0.000840

Gnomad OTH exome

AF:

0.00578

GnomAD4 exome

AF:

0.0118

AC:

14040

AN:

1193490

Hom.:

1455

Cov.:

AF XY:

0.0128

AC XY:

7521

AN XY:

585888

show subpopulations

African (AFR)

AF:

0.0646

AC:

1664

AN:

25744

American (AMR)

AF:

0.0144

AC:

534

AN:

37074

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

257

AN:

19062

East Asian (EAS)

AF:

0.125

AC:

2847

AN:

22760

South Asian (SAS)

AF:

0.0483

AC:

2505

AN:

51854

European-Finnish (FIN)

AF:

0.0462

AC:

1380

AN:

29874

Middle Eastern (MID)

AF:

0.0132

AC:

AN:

2722

European-Non Finnish (NFE)

AF:

0.00427

AC:

4083

AN:

957324

Other (OTH)

AF:

0.0156

AC:

734

AN:

47076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

661

1323

1984

2646

3307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0324

AC:

2913

AN:

90034

Hom.:

555

Cov.:

AF XY:

0.0314

AC XY:

1345

AN XY:

42788

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.104

AC:

2116

AN:

20312

American (AMR)

AF:

0.0165

AC:

169

AN:

10238

Ashkenazi Jewish (ASJ)

AF:

0.00858

AC:

AN:

2214

East Asian (EAS)

AF:

0.0163

AC:

AN:

1778

South Asian (SAS)

AF:

0.0129

AC:

AN:

2322

European-Finnish (FIN)

AF:

0.0181

AC:

AN:

4634

Middle Eastern (MID)

AF:

0.00926

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00928

AC:

430

AN:

46338

Other (OTH)

AF:

0.0228

AC:

AN:

1316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

120

240

361

481

601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ESP6500AA

AF:

0.0348

AC:

151

ESP6500EA

AF:

0.000599

AC:

ExAC

AF:

0.00602

AC:

707

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 31, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.25

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.00040

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.94

PhyloP100

-0.35

PrimateAI

Uncertain

0.51

PROVEAN

Benign

1.6

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

0.97

Polyphen

0.0

MutPred

0.19

Loss of sheet (P = 0.0011);

MVP

0.41

MPC

1.8

ClinPred

0.000052

GERP RS

0.25

Varity_R

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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NM_002186.3:c.991G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over