NM_175726.4:c.367+1203T>C

Variant names:

• chr3-3100489-A-G
• rs9831572
• NM_175726.4:c.367+1203T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175726.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	NM_175726.4	MANE Select	c.367+1203T>C		intron	N/A	NP_783853.1
	IL5RA	NM_000564.5		c.367+1203T>C		intron	N/A	NP_000555.2
	IL5RA	NM_001243099.2		c.367+1203T>C		intron	N/A	NP_001230028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	ENST00000446632.7	TSL:5 MANE Select	c.367+1203T>C		intron	N/A	ENSP00000412209.2
	IL5RA	ENST00000256452.7	TSL:1	c.367+1203T>C		intron	N/A	ENSP00000256452.3
	IL5RA	ENST00000311981.12	TSL:1	c.367+1203T>C		intron	N/A	ENSP00000309196.8

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

African (AFR) AF: 0.687 AC: 28496 AN: 41490

American (AMR) AF: 0.677 AC: 10345 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3685 AN: 5166

South Asian (SAS) AF: 0.843 AC: 4063 AN: 4822

European-Finnish (FIN) AF: 0.637 AC: 6726 AN: 10566

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45622 AN: 67972

Other (OTH) AF: 0.698 AC: 1475 AN: 2112

Alfa AF: 0.679 Hom.: 12402

Bravo AF: 0.683

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.36
DANN	Benign	0.87
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9831572; hg19: chr3-3142173;