rs17026370

Positions:

• chr3-3083757-G-T

Variant summary

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

The NM_175726.4(IL5RA):​c.995-7130C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 152,242 control chromosomes in the GnomAD database, including 1,442 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 0.092 (1442 hom., cov: 33)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL5RA	NM_175726.4	c.995-7130C>A		intron_variant		ENST00000446632.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL5RA	ENST00000446632.7	c.995-7130C>A		intron_variant		5	NM_175726.4	P2
IL5RA	ENST00000256452.7	c.995-7130C>A		intron_variant		1		P2
IL5RA	ENST00000418488.6	c.710-7130C>A		intron_variant		5
IL5RA	ENST00000438560.5	c.995-7130C>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13891 AN: 152124 Hom.: 1431 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0916 AC: 13945 AN: 152242 Hom.: 1442 Cov.: 33 AF XY: 0.0907 AC XY: 6752 AN XY: 74424

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0541

Gnomad4 FIN AF: 0.0394

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0860

Alfa AF: 0.0503 Hom.: 318

Bravo AF: 0.0983

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.082
DANN	Benign	0.34

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: rs17026370; hg19: chr3-3125441;