5-135894120-C-A

Variant names:

• chr5-135894120-C-A
• NM_000590.2:c.215G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000590.2(IL9):​c.215G>T​(p.Arg72Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL9 NM_000590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000590.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL9	NM_000590.2	MANE Select	c.215G>T	p.Arg72Ile	missense	Exon 4 of 5	NP_000581.1	P15248

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL9	ENST00000274520.2	TSL:1 MANE Select	c.215G>T	p.Arg72Ile	missense	Exon 4 of 5	ENSP00000274520.1	P15248

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0048	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0040	B
Vest4		0.36
MutPred		0.67		Loss of disorder (P = 0.0124)
MVP		0.70
MPC		0.48
ClinPred		0.38	T
GERP RS		5.8
Varity_R		0.075
gMVP		0.58
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr5-135229809;