rs17881144

Positions:

• chr3-3103687-A-T

Variant summary

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

The NM_175726.4(IL5RA):​c.83-867T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 152,298 control chromosomes in the GnomAD database, including 234 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 0.040 (234 hom., cov: 33)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL5RA	NM_175726.4	c.83-867T>A		intron_variant		ENST00000446632.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL5RA	ENST00000446632.7	c.83-867T>A		intron_variant		5	NM_175726.4	P2

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6087 AN: 152180 Hom.: 233 Cov.: 33

Gnomad AFR AF: 0.00830

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0400 AC: 6090 AN: 152298 Hom.: 234 Cov.: 33 AF XY: 0.0447 AC XY: 3329 AN XY: 74468

Gnomad4 AFR AF: 0.00825

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.0740

Gnomad4 SAS AF: 0.0305

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.0370

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0438 Hom.: 26

Bravo AF: 0.0385

Asia WGS AF: 0.0460 AC: 160 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.62

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: rs17881144; hg19: chr3-3145371;