rs11713419

Positions:

• chr3-3108583-A-G

Variant summary

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

The NM_175726.4(IL5RA):​c.-37T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,196 control chromosomes in the GnomAD database, including 2,994 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 0.19 (2993 hom., cov: 33)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: IL5RA NM_175726.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.-37T>C		5_prime_UTR_variant	2/12	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7	c.-37T>C		5_prime_UTR_variant	2/12	5	NM_175726.4	ENSP00000412209	P2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28798 AN: 152058 Hom.: 2987 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.250 AC: 5 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 4 AN XY: 16

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.189 AC: 28837 AN: 152176 Hom.: 2993 Cov.: 33 AF XY: 0.186 AC XY: 13857 AN XY: 74392

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.165

Alfa AF: 0.157 Hom.: 3430

Bravo AF: 0.192

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	-0.89
CADD	Benign	0.85
DANN	Benign	0.42

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: rs11713419; hg19: chr3-3150267;