5-135892432-A-G

Variant names:

• chr5-135892432-A-G
• rs752902305
• NM_000590.2:c.394T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000590.2(IL9):​c.394T>C​(p.Phe132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,612,416 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F132Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (2 hom.)
• Consequence: IL9 NM_000590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08883244).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.394T>C	p.Phe132Leu	missense	Exon 5 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.394T>C	p.Phe132Leu	missense	Exon 5 of 5	ENSP00000274520.1	P15248

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000718 AC: 18 AN: 250762 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1460320 Hom.: 2 Cov.: 29 AF XY: 0.0000674 AC XY: 49 AN XY: 726470

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.000112 AC: 5 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000733 AC: 63 AN: 85996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110982

Other (OTH) AF: 0.0000497 AC: 3 AN: 60344

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.0000655 AC: 1 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000824 AC: 10

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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.045
Sift	Benign	0.061	T
Sift4G	Benign	0.091	T
Polyphen		0.28	B
Vest4		0.26
MutPred		0.61		Loss of methylation at K134 (P = 0.0904)
MVP		0.38
MPC		0.85
ClinPred		0.17	T
GERP RS		3.1
Varity_R		0.25
gMVP		0.34
Mutation Taster		=93/7	polymorphism

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: rs752902305; hg19: chr5-135228121;