chr5-135892464-G-C

Variant names:

• chr5-135892464-G-C
• rs201509284
• NM_000590.2:c.362C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000590.2(IL9):​c.362C>G​(p.Ala121Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A121V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL9 NM_000590.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23623922).

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.362C>G	p.Ala121Gly	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.362C>G	p.Ala121Gly	missense	Exon 5 of 5	ENSP00000274520.1	P15248

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461042 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726824

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111482

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.91
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.060
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.010	D
Polyphen		0.25	B
Vest4		0.073
MutPred		0.54		Gain of loop (P = 0.0435)
MVP		0.24
MPC		0.29
ClinPred		0.14	T
GERP RS		-2.9
Varity_R		0.074
gMVP		0.26
Mutation Taster		=95/5	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: rs201509284; hg19: chr5-135228153;