rs6771148

Positions:

• chr3-3101583-G-C
• chr3-3101583-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.367+109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,083,554 control chromosomes in the GnomAD database, including 328,581 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 0.79 (48117 hom., cov: 33)
  • Exomes 𝑓: 0.77 (280464 hom.)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.367+109C>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.367+109C>G		intron_variant		5	NM_175726.4	ENSP00000412209	P2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120734 AN: 152050 Hom.: 48059 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.807

GnomAD4 exome AF: 0.774 AC: 721235 AN: 931386 Hom.: 280464 AF XY: 0.778 AC XY: 367114 AN XY: 471812

Gnomad4 AFR exome AF: 0.835

Gnomad4 AMR exome AF: 0.853

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.900

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.794 AC: 120852 AN: 152168 Hom.: 48117 Cov.: 33 AF XY: 0.797 AC XY: 59266 AN XY: 74384

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.809

Alfa AF: 0.777 Hom.: 5752

Bravo AF: 0.799

Asia WGS AF: 0.864 AC: 3003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.38

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: rs6771148; hg19: chr3-3143267; COSMIC: COSV56525222; COSMIC: COSV56525222;