rs1859430

Positions:

• chr5-135894824-G-A

Variant summary

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

The NM_000590.2(IL9):​c.183+616C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,118 control chromosomes in the GnomAD database, including 3,162 homozygotes. 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 0.20 (3162 hom., cov: 32)
• Consequence: IL9 NM_000590.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

Genes affected

IL9 (HGNC:6029): (interleukin 9) The protein encoded by this gene is a cytokine that acts as a regulator of a variety of hematopoietic cells. This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin 9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness. [provided by RefSeq, Jul 2008]

LOC124901074 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL9	NM_000590.2	c.183+616C>T		intron_variant		ENST00000274520.2	NP_000581.1
LOC124901074	XR_007058947.1	n.509-874G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL9	ENST00000274520.2	c.183+616C>T		intron_variant		1	NM_000590.2	ENSP00000274520	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30058 AN: 152000 Hom.: 3154 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.198 AC: 30097 AN: 152118 Hom.: 3162 Cov.: 32 AF XY: 0.195 AC XY: 14504 AN XY: 74364

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.190

Alfa AF: 0.188 Hom.: 5641

Bravo AF: 0.196

Asia WGS AF: 0.115 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.48

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: rs1859430; hg19: chr5-135230513;