rs4054760

chr3-3109984-G-A

Variant summary

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

The NM_175726.4(IL5RA):c.-185C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,108 control chromosomes in the GnomAD database, including 5,576 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 0.26 (5576 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL5RA NM_175726.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL5RA	NM_175726.4	c.-185C>T		5_prime_UTR_variant	1/12	ENST00000446632.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL5RA	ENST00000446632.7	c.-185C>T		5_prime_UTR_variant	1/12	5	NM_175726.4	P2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39953 AN: 151990 Hom.: 5567 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.263 AC: 39984 AN: 152108 Hom.: 5576 Cov.: 32 AF XY: 0.259 AC XY: 19260 AN XY: 74358

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.250

Alfa AF: 0.268 Hom.: 6696

Bravo AF: 0.260

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.6
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4054760; hg19: chr3-3151668;