rs9869655

Variant names:

• chr3-3080173-G-A
• rs9869655
• NM_175726.4:c.995-3546C>T

Variant summary

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

The NM_175726.4(IL5RA):​c.995-3546C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,208 control chromosomes in the GnomAD database, including 1,616 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 0.14 (1616 hom., cov: 33)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 4 publications found

Genes affected

IL5RA (HGNC:6017): (interleukin 5 receptor subunit alpha) The protein encoded by this gene is an interleukin 5 specific subunit of a heterodimeric cytokine receptor. The receptor is comprised of a ligand specific alpha subunit and a signal transducing beta subunit shared by the receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2/GM-CSF), and interleukin 5 (IL5). The binding of this protein to IL5 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of IL5. This protein has been found to interact with syndecan binding protein (syntenin), which is required for IL5 mediated activation of the transcription factor SOX4. Several alternatively spliced transcript variants encoding four distinct isoforms have been reported. [provided by RefSeq, Jul 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.995-3546C>T		intron_variant	Intron 9 of 11	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7	c.995-3546C>T		intron_variant	Intron 9 of 11	5	NM_175726.4	ENSP00000412209.2
IL5RA	ENST00000256452.7	c.995-3546C>T		intron_variant	Intron 10 of 12	1		ENSP00000256452.3
IL5RA	ENST00000438560.5	c.995-3546C>T		intron_variant	Intron 9 of 10	2		ENSP00000390753.1
IL5RA	ENST00000418488.6	c.710-3546C>T		intron_variant	Intron 8 of 10	5		ENSP00000388858.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21089 AN: 152090 Hom.: 1612 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.139 AC: 21103 AN: 152208 Hom.: 1616 Cov.: 33 AF XY: 0.140 AC XY: 10412 AN XY: 74408

African (AFR) AF: 0.170 AC: 7044 AN: 41522

American (AMR) AF: 0.115 AC: 1765 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1357 AN: 5186

South Asian (SAS) AF: 0.227 AC: 1093 AN: 4812

European-Finnish (FIN) AF: 0.0961 AC: 1018 AN: 10596

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8051 AN: 68012

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.131 Hom.: 1019

Bravo AF: 0.140

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs9869655; hg19: chr3-3121857;