rs1153459

Positions:

• chr3-3116801-T-C

Variant summary

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

The ENST00000445701.5(IL5RA):​c.-145-8110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,548 control chromosomes in the GnomAD database, including 15,898 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 0.45 (15898 hom., cov: 30)
• Consequence: IL5RA ENST00000445701.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

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]

(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 (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.3116801T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000445701.5	c.-145-8110A>G		intron_variant		3		ENSP00000398117.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67510 AN: 151434 Hom.: 15901 Cov.: 30

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.446 AC: 67517 AN: 151548 Hom.: 15898 Cov.: 30 AF XY: 0.444 AC XY: 32862 AN XY: 74018

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.454

Alfa AF: 0.492 Hom.: 17080

Bravo AF: 0.429

Asia WGS AF: 0.265 AC: 922 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	4.2
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1153459; hg19: chr3-3158485;