3-3088961-T-C

Position:

• chr3-3088961-T-C

Variant summary

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

The NM_175726.4(IL5RA):​c.994+3263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,214 control chromosomes in the GnomAD database, including 757 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 0.080 (757 hom., cov: 32)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.994+3263A>G		intron_variant		ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7	c.994+3263A>G		intron_variant		5	NM_175726.4	ENSP00000412209	P2
IL5RA	ENST00000256452.7	c.994+3263A>G		intron_variant		1		ENSP00000256452	P2
IL5RA	ENST00000418488.6	c.709+8909A>G		intron_variant		5		ENSP00000388858
IL5RA	ENST00000438560.5	c.994+3263A>G		intron_variant		2		ENSP00000390753	A2

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12217 AN: 152096 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.0802 AC: 12212 AN: 152214 Hom.: 757 Cov.: 32 AF XY: 0.0848 AC XY: 6309 AN XY: 74420

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0556

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.0912 Hom.: 1504

Bravo AF: 0.0696

Asia WGS AF: 0.213 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.5
DANN	Benign	0.58

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: rs3804795; hg19: chr3-3130645;