3-3100489-A-G

Position:

• chr3-3100489-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.367+1203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,086 control chromosomes in the GnomAD database, including 35,539 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 0.68 (35539 hom., cov: 32)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL5RA	NM_175726.4	c.367+1203T>C		intron_variant		ENST00000446632.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL5RA	ENST00000446632.7	c.367+1203T>C		intron_variant		5	NM_175726.4	P2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103699 AN: 151968 Hom.: 35508 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.682 AC: 103787 AN: 152086 Hom.: 35539 Cov.: 32 AF XY: 0.684 AC XY: 50899 AN XY: 74362

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.698

Alfa AF: 0.674 Hom.: 6449

Bravo AF: 0.683

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.36
DANN	Benign	0.87

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: rs9831572; hg19: chr3-3142173;