rs340833

Variant names:

• chr3-3069774-G-A
• rs340833
• NM_175726.4:c.*451C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-3069774-G-A
• chr3-3069774-G-C

Variant summary

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

The NM_175726.4(IL5RA):​c.*451C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 157,046 control chromosomes in the GnomAD database, including 19,446 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 0.49 (18889 hom., cov: 31)
  • Exomes 𝑓: 0.46 (557 hom.)
• Consequence: IL5RA NM_175726.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.*451C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632	c.*451C>T		3_prime_UTR_variant	Exon 12 of 12	5	NM_175726.4	ENSP00000412209.2
IL5RA	ENST00000256452	c.*451C>T		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000256452.3
IL5RA	ENST00000438560	c.*492C>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000390753.1
IL5RA	ENST00000418488	c.*451C>T		3_prime_UTR_variant	Exon 11 of 11	5		ENSP00000388858.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74931 AN: 151724 Hom.: 18852 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.463 AC: 2407 AN: 5204 Hom.: 557 Cov.: 0 AF XY: 0.466 AC XY: 1260 AN XY: 2706

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.494 AC: 75014 AN: 151842 Hom.: 18889 Cov.: 31 AF XY: 0.493 AC XY: 36599 AN XY: 74196

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.463

Alfa AF: 0.502 Hom.: 26491

Bravo AF: 0.487

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.77

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: rs340833; hg19: chr3-3111458;