rs17882210

Variant names:

• chr3-3076814-A-G
• rs17882210
• NM_175726.4:c.995-187T>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.995-187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,070 control chromosomes in the GnomAD database, including 10,912 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 0.38 (10912 hom., cov: 32)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.995-187T>C		intron_variant	Intron 9 of 11	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7	c.995-187T>C		intron_variant	Intron 9 of 11	5	NM_175726.4	ENSP00000412209.2
IL5RA	ENST00000256452.7	c.995-187T>C		intron_variant	Intron 10 of 12	1		ENSP00000256452.3
IL5RA	ENST00000438560.5	c.995-187T>C		intron_variant	Intron 9 of 10	2		ENSP00000390753.1
IL5RA	ENST00000418488.6	c.710-187T>C		intron_variant	Intron 8 of 10	5		ENSP00000388858.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57045 AN: 151952 Hom.: 10915 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.375 AC: 57041 AN: 152070 Hom.: 10912 Cov.: 32 AF XY: 0.370 AC XY: 27535 AN XY: 74344

African (AFR) AF: 0.327 AC: 13553 AN: 41474

American (AMR) AF: 0.313 AC: 4783 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3470

East Asian (EAS) AF: 0.338 AC: 1748 AN: 5174

South Asian (SAS) AF: 0.391 AC: 1887 AN: 4820

European-Finnish (FIN) AF: 0.349 AC: 3694 AN: 10578

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28500 AN: 67960

Other (OTH) AF: 0.383 AC: 805 AN: 2104

Alfa AF: 0.396 Hom.: 1863

Bravo AF: 0.370

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.47
PhyloP100		0.070
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: rs17882210; hg19: chr3-3118498;