X-155997942-T-G

Variant names:

• chrX-155997942-T-G
• rs3093457
• NM_002186.3:c.28+155T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002186.3(IL9R):​c.28+155T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,808 control chromosomes in the GnomAD database, including 15,598 homozygotes. There are 32,914 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15598 hom., 32914 hem., cov: 31)
• Consequence: IL9R NM_002186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002186.3. 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
	IL9R	NM_002186.3	MANE Select	c.28+155T>G		intron	N/A	NP_002177.2
	IL9R	NM_176786.2		c.44+155T>G		intron	N/A	NP_789743.2	Q01113-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL9R	ENST00000244174.11	TSL:1 MANE Select	c.28+155T>G		intron	N/A	ENSP00000244174.5	Q01113-1
	IL9R	ENST00000369423.8	TSL:1	c.44+155T>G		intron	N/A	ENSP00000358431.2	Q01113-3
	IL9R	ENST00000489233.6	TSL:1	n.54+155T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65931 AN: 151688 Hom.: 15578 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.404

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 65986 AN: 151808 Hom.: 15598 Cov.: 31 AF XY: 0.444 AC XY: 32914 AN XY: 74134

African (AFR) AF: 0.573 AC: 23696 AN: 41378

American (AMR) AF: 0.359 AC: 5481 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1492 AN: 3464

East Asian (EAS) AF: 0.692 AC: 3567 AN: 5152

South Asian (SAS) AF: 0.532 AC: 2554 AN: 4804

European-Finnish (FIN) AF: 0.573 AC: 6042 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21857 AN: 67914

Other (OTH) AF: 0.398 AC: 838 AN: 2106

Bravo AF: 0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.64
PhyloP100		-0.080
PromoterAI		-0.040	Neutral

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: rs3093457; hg19: chrX-155227607; COSMIC: COSV99729966;