rs3093496

Variant names:

• chrX-156003570-G-A
• rs3093496
• NM_002186.3:c.254+10G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002186.3(IL9R):​c.254+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,610,980 control chromosomes in the GnomAD database, including 318 homozygotes. There are 3,290 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (163 hom., 1726 hem., cov: 33)
  • Exomes 𝑓: 0.0025 (155 hom. 1564 hem.)
• Consequence: IL9R NM_002186.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-156003570-G-A is Benign according to our data. Variant chrX-156003570-G-A is described in ClinVar as Benign. ClinVar VariationId is 785714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0832 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.254+10G>A		intron	N/A	NP_002177.2
	IL9R	NM_176786.2		c.395+10G>A		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.254+10G>A		intron	N/A	ENSP00000244174.5	Q01113-1
	IL9R	ENST00000369423.8	TSL:1	c.395+10G>A		intron	N/A	ENSP00000358431.2	Q01113-3
	IL9R	ENST00000858259.1		c.29-107G>A		intron	N/A	ENSP00000528318.1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3695 AN: 152194 Hom.: 161 Cov.: 33

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00611 AC: 1533 AN: 250894 AF XY: 0.00434

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00246 AC: 3584 AN: 1458668 Hom.: 155 Cov.: 32 AF XY: 0.00216 AC XY: 1564 AN XY: 725698

African (AFR) AF: 0.0908 AC: 3032 AN: 33396

American (AMR) AF: 0.00344 AC: 154 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000221 AC: 19 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00212 AC: 12 AN: 5656

European-Non Finnish (NFE) AF: 0.0000469 AC: 52 AN: 1109262

Other (OTH) AF: 0.00523 AC: 315 AN: 60262

GnomAD4 genome AF: 0.0243 AC: 3707 AN: 152312 Hom.: 163 Cov.: 33 AF XY: 0.0232 AC XY: 1726 AN XY: 74456

African (AFR) AF: 0.0855 AC: 3554 AN: 41558

American (AMR) AF: 0.00699 AC: 107 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Bravo AF: 0.0276

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.79
PhyloP100		-0.35

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: rs3093496; hg19: chrX-155233235;