dbSNP rs2069885: IL9:p.Thr117Met (chr5-135892476-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000590.2(IL9):c.350C>T(p.Thr117Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,611,616 control chromosomes in the GnomAD database, including 13,040 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1232 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11808 hom. )

Consequence

IL9
NM_000590.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Variant links:

Genes affected

IL9 (HGNC:6029): (interleukin 9) The protein encoded by this gene is a cytokine that acts as a regulator of a variety of hematopoietic cells. This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin 9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness. [provided by RefSeq, Jul 2008]

IL9 links:

LOC124901074 (HGNC:):

LOC124901074 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014887452).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL9	NM_000590.2 link	c.350C>T	p.Thr117Met	missense_variant	Exon 5 of 5	ENST00000274520.2	NP_000581.1	P15248
LOC124901074	XR_007058947.1 link	n.381G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL9	ENST00000274520.2 link	c.350C>T	p.Thr117Met	missense_variant	Exon 5 of 5	1	NM_000590.2	ENSP00000274520.1		P15248

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18816

AN:

151862

Hom.:

1230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.0836

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.111

AC:

27854

AN:

250330

Hom.:

1866

AF XY:

0.113

AC XY:

15314

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.0548

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.123

AC:

179266

AN:

1459636

Hom.:

11808

Cov.:

AF XY:

0.123

AC XY:

89148

AN XY:

726098

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0575

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.000958

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.124

AC:

18827

AN:

151980

Hom.:

1232

Cov.:

AF XY:

0.123

AC XY:

9168

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0834

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.00175

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.126

Hom.:

2891

Bravo

AF:

0.118

TwinsUK

AF:

0.136

AC:

505

ALSPAC

AF:

0.122

AC:

469

ESP6500AA

AF:

0.129

AC:

570

ESP6500EA

AF:

0.136

AC:

1171

ExAC

AF:

0.116

AC:

14135

Asia WGS

AF:

0.0730

AC:

257

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.0

DANN

Benign

0.83

DEOGEN2

Uncertain

0.46

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.85

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.019

Sift

Benign

0.16

Sift4G

Benign

0.23

Polyphen

0.33

Vest4

0.018

MPC

0.28

ClinPred

0.014

GERP RS

-1.6

Varity_R

0.054

gMVP

0.49

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over