rs4054760

Variant names:

• chr3-3109984-G-A
• rs4054760
• NM_175726.4:c.-185C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175726.4(IL5RA):​c.-185C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,108 control chromosomes in the GnomAD database, including 5,576 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 0.26 (5576 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL5RA NM_175726.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.-185C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7	c.-185C>T		5_prime_UTR_variant	Exon 1 of 12	5	NM_175726.4	ENSP00000412209.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39953 AN: 151990 Hom.: 5567 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.263 AC: 39984 AN: 152108 Hom.: 5576 Cov.: 32 AF XY: 0.259 AC XY: 19260 AN XY: 74358

African (AFR) AF: 0.263 AC: 10887 AN: 41474

American (AMR) AF: 0.272 AC: 4154 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3472

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5184

South Asian (SAS) AF: 0.195 AC: 942 AN: 4822

European-Finnish (FIN) AF: 0.303 AC: 3205 AN: 10584

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19126 AN: 67978

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.268 Hom.: 9496

Bravo AF: 0.260

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.73
PhyloP100		0.46
PromoterAI		0.065	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4054760; hg19: chr3-3151668;