chrX-156009937-G-T

Variant names:

• chrX-156009937-G-T
• NM_002186.3:c.1094G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002186.3(IL9R):​c.1094G>T​(p.Arg365Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 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. R365H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL9R NM_002186.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

Genes affected

IL9R (HGNC:6030): (interleukin 9 receptor) The protein encoded by this gene is a cytokine receptor that specifically mediates the biological effects of interleukin 9 (IL9). The functional IL9 receptor complex requires this protein as well as the interleukin 2 receptor, gamma (IL2RG), a common gamma subunit shared by the receptors of many different cytokines. The ligand binding of this receptor leads to the activation of various JAK kinases and STAT proteins, which connect to different biologic responses. This gene is located at the pseudoautosomal regions of X and Y chromosomes. Genetic studies suggested an association of this gene with the development of asthma. Multiple pseudogenes on chromosome 9, 10, 16, and 18 have been described. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000270726 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038403958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL9R	NM_002186.3	c.1094G>T	p.Arg365Leu	missense_variant	Exon 9 of 9	ENST00000244174.11	NP_002177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL9R	ENST00000244174.11	c.1094G>T	p.Arg365Leu	missense_variant	Exon 9 of 9	1	NM_002186.3	ENSP00000244174.5
IL9R	ENST00000369423.7	c.*85G>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000358431.2
ENSG00000270726	ENST00000483543.7	n.433+2330G>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1375540 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 684008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.026
DANN	Benign	0.44
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.00060	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.018
Sift	Benign	0.65	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.078
MutPred		0.25		Gain of catalytic residue at R365 (P = 0.0222);
MVP		0.23
MPC		1.9
ClinPred		0.056	T
GERP RS		0.20
Varity_R		0.047

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-155239602;