NM_002186.3:c.1094G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002186.3(IL9R):c.1094G>A(p.Arg365His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.029 ( 34 hom., 1513 hem., cov: 19)

Exomes 𝑓: 0.018 ( 3965 hom. 13382 hem. )

Failed GnomAD Quality Control

Consequence

IL9R
NM_002186.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.936

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004162729).

BP6

Variant X-156009937-G-A is Benign according to our data. Variant chrX-156009937-G-A is described in ClinVar as [Benign]. Clinvar id is 771064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0286 (3012/105206) while in subpopulation SAS AF= 0.0443 (123/2778). AF 95% confidence interval is 0.0379. There are 34 homozygotes in gnomad4. There are 1513 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL9R	NM_002186.3 link	c.1094G>A	p.Arg365His	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.1094G>A	p.Arg365His	missense_variant	Exon 9 of 9	1	NM_002186.3	ENSP00000244174.5	Q01113-1
IL9R	ENST00000369423.7 link	c.*85G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000358431.2	Q01113-3
ENSG00000270726	ENST00000483543.7 link	n.433+2330G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

3010

AN:

105112

Hom.:

Cov.:

AF XY:

0.0299

AC XY:

1506

AN XY:

50414

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.0415

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.0448

Gnomad FIN

AF:

0.0722

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0231

GnomAD3 exomes

AF:

0.0140

AC:

3225

AN:

229600

Hom.:

814

AF XY:

0.0139

AC XY:

1726

AN XY:

124330

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.00783

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.0159

Gnomad SAS exome

AF:

0.0411

Gnomad FIN exome

AF:

0.00544

Gnomad NFE exome

AF:

0.00819

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0177

AC:

23727

AN:

1341980

Hom.:

3965

Cov.:

AF XY:

0.0201

AC XY:

13382

AN XY:

665770

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.00970

Gnomad4 ASJ exome

AF:

0.0377

Gnomad4 EAS exome

AF:

0.0568

Gnomad4 SAS exome

AF:

0.0775

Gnomad4 FIN exome

AF:

0.0630

Gnomad4 NFE exome

AF:

0.00933

Gnomad4 OTH exome

AF:

0.0262

GnomAD4 genome

AF:

0.0286

AC:

3012

AN:

105206

Hom.:

Cov.:

AF XY:

0.0300

AC XY:

1513

AN XY:

50508

show subpopulations

Gnomad4 AFR

AF:

0.0370

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.0249

Gnomad4 SAS

AF:

0.0443

Gnomad4 FIN

AF:

0.0722

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0221

ExAC

AF:

0.00518

AC:

612

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

- -

May 24, 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

-0.61

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.045

DANN

Benign

0.40

DEOGEN2

Benign

0.0096

FATHMM_MKL

Benign

0.00045

LIST_S2

Benign

0.25

M_CAP

Benign

0.00085

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.90

PrimateAI

Benign

0.36

PROVEAN

Benign

0.92

REVEL

Benign

0.019

Sift

Benign

0.55

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.029

MPC

1.9

ClinPred

0.0011

GERP RS

0.20

Varity_R

0.019

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over