rs3093467

Variant names:

• chrX-155999524-T-C
• rs3093467
• NM_002186.3:c.28+1737T>C

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+1737T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,778 control chromosomes in the GnomAD database, including 20,454 homozygotes. There are 36,412 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 0.49 (20454 hom., 36412 hem., cov: 31)
• Consequence: IL9R NM_002186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL9R	NM_002186.3	c.28+1737T>C		intron_variant	Intron 1 of 8	ENST00000244174.11	NP_002177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL9R	ENST00000244174.11	c.28+1737T>C		intron_variant	Intron 1 of 8	1	NM_002186.3	ENSP00000244174.5
IL9R	ENST00000369423.8	c.44+1737T>C		intron_variant	Intron 1 of 8	1		ENSP00000358431.2
IL9R	ENST00000489233.6	n.54+1737T>C		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73742 AN: 151658 Hom.: 20413 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.486 AC: 73829 AN: 151778 Hom.: 20454 Cov.: 31 AF XY: 0.491 AC XY: 36412 AN XY: 74160

African (AFR) AF: 0.742 AC: 30718 AN: 41390

American (AMR) AF: 0.373 AC: 5683 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3464

East Asian (EAS) AF: 0.634 AC: 3266 AN: 5150

South Asian (SAS) AF: 0.555 AC: 2672 AN: 4812

European-Finnish (FIN) AF: 0.574 AC: 6049 AN: 10540

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22590 AN: 67870

Other (OTH) AF: 0.431 AC: 908 AN: 2106

Bravo AF: 0.481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-2.4

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: rs3093467; hg19: chrX-155229189;