chr5-135894120-C-A

Position:

• chr5-135894120-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL9	NM_000590.2	c.215G>T	p.Arg72Ile	missense_variant	4/5	ENST00000274520.2	NP_000581.1
LOC124901074	XR_007058947.1	n.508+1517C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL9	ENST00000274520.2	c.215G>T	p.Arg72Ile	missense_variant	4/5	1	NM_000590.2	ENSP00000274520	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.215G>T (p.R72I) alteration is located in exon 4 (coding exon 4) of the IL9 gene. This alteration results from a G to T substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-135229809;