rs2069885

Variant names:

• chr5-135892476-G-A
• rs2069885
• NM_000590.2:c.350C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-135892476-G-A
• chr5-135892476-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 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. T117A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1232 hom., cov: 31)
  • Exomes 𝑓: 0.12 (11808 hom.)
• Consequence: IL9 NM_000590.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 60 publications found

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]

LOC124901074 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.350C>T	p.Thr117Met	missense_variant	Exon 5 of 5	ENST00000274520.2	NP_000581.1
LOC124901074	XR_007058947.1	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	c.350C>T	p.Thr117Met	missense_variant	Exon 5 of 5	1	NM_000590.2	ENSP00000274520.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18816 AN: 151862 Hom.: 1230 Cov.: 31

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

GnomAD2 exomes AF: 0.111 AC: 27854 AN: 250330 AF XY: 0.113

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 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.: 31 AF XY: 0.123 AC XY: 89148 AN XY: 726098

African (AFR) AF: 0.123 AC: 4099 AN: 33384

American (AMR) AF: 0.0575 AC: 2558 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 4170 AN: 26038

East Asian (EAS) AF: 0.000958 AC: 38 AN: 39686

South Asian (SAS) AF: 0.108 AC: 9255 AN: 85852

European-Finnish (FIN) AF: 0.150 AC: 7985 AN: 53318

Middle Eastern (MID) AF: 0.129 AC: 744 AN: 5762

European-Non Finnish (NFE) AF: 0.129 AC: 143240 AN: 1110816

Other (OTH) AF: 0.119 AC: 7177 AN: 60258

GnomAD4 genome AF: 0.124 AC: 18827 AN: 151980 Hom.: 1232 Cov.: 31 AF XY: 0.123 AC XY: 9168 AN XY: 74278

African (AFR) AF: 0.129 AC: 5335 AN: 41466

American (AMR) AF: 0.0834 AC: 1274 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3468

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5152

South Asian (SAS) AF: 0.101 AC: 483 AN: 4792

European-Finnish (FIN) AF: 0.150 AC: 1578 AN: 10552

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9112 AN: 67960

Other (OTH) AF: 0.107 AC: 226 AN: 2112

Alfa AF: 0.126 Hom.: 4067

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	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.0
DANN	Benign	0.83
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	L
PhyloP100		0.029
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.019
Sift	Benign	0.16	T
Sift4G	Benign	0.23	T
Polyphen		0.33	B
Vest4		0.018
MPC		0.28
ClinPred		0.014	T
GERP RS		-1.6
Varity_R		0.054
gMVP		0.49
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2069885; hg19: chr5-135228165; COSMIC: COSV50853368; COSMIC: COSV50853368;