rs731476

Positions:

• chrX-155999338-G-A
• chrX-155999338-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002186.3(IL9R):​c.28+1551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,798 control chromosomes in the GnomAD database, including 19,769 homozygotes. There are 35,903 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 0.48 (19769 hom., 35903 hem., cov: 31)
• Consequence: IL9R NM_002186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL9R	NM_002186.3	c.28+1551G>A		intron_variant		ENST00000244174.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL9R	ENST00000244174.11	c.28+1551G>A		intron_variant		1	NM_002186.3	P1
IL9R	ENST00000369423.7	c.44+1551G>A		intron_variant		1
IL9R	ENST00000489233.6	n.54+1551G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72679 AN: 151678 Hom.: 19736 Cov.: 31 AF XY: 0.484 AC XY: 35809 AN XY: 74006

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.479 AC: 72758 AN: 151798 Hom.: 19769 Cov.: 31 AF XY: 0.484 AC XY: 35903 AN XY: 74134

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.422

Bravo AF: 0.474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.27

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

LitVar

Other links and lift over

dbSNP: rs731476; hg19: chrX-155229003;