NM_000590.2:c.350C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000590.2(IL9):​c.350C>G​(p.Thr117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T117M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: IL9 NM_000590.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25651968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL9	NM_000590.2	c.350C>G	p.Thr117Arg	missense_variant	Exon 5 of 5	ENST00000274520.2	NP_000581.1
LOC124901074	XR_007058947.1	n.381G>C		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>G	p.Thr117Arg	missense_variant	Exon 5 of 5	1	NM_000590.2	ENSP00000274520.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.4
DANN	Benign	0.83
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.044
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.84	P
Vest4		0.28
MutPred		0.50		Gain of phosphorylation at T116 (P = 0.1099);
MVP		0.46
MPC		0.39
ClinPred		0.87	D
GERP RS		-1.6
Varity_R		0.41
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2069885; hg19: chr5-135228165;