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. The variant received -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
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	NM_175726.4	MANE Select	c.*451C>T		3_prime_UTR	Exon 12 of 12	NP_783853.1	Q01344-1
	IL5RA	NM_000564.5		c.*451C>T		3_prime_UTR	Exon 13 of 13	NP_000555.2
	IL5RA	NM_001243099.2		c.*492C>T		3_prime_UTR	Exon 11 of 11	NP_001230028.1	Q01344-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	ENST00000446632.7	TSL:5 MANE Select	c.*451C>T		3_prime_UTR	Exon 12 of 12	ENSP00000412209.2	Q01344-1
	IL5RA	ENST00000256452.7	TSL:1	c.*451C>T		3_prime_UTR	Exon 13 of 13	ENSP00000256452.3	Q01344-1
	IL5RA	ENST00000438560.5	TSL:2	c.*492C>T		3_prime_UTR	Exon 11 of 11	ENSP00000390753.1	Q01344-4

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

African (AFR) AF: 0.414 AC: 63 AN: 152

American (AMR) AF: 0.451 AC: 73 AN: 162

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 75 AN: 188

East Asian (EAS) AF: 0.220 AC: 77 AN: 350

South Asian (SAS) AF: 0.409 AC: 27 AN: 66

European-Finnish (FIN) AF: 0.480 AC: 191 AN: 398

Middle Eastern (MID) AF: 0.438 AC: 7 AN: 16

European-Non Finnish (NFE) AF: 0.491 AC: 1743 AN: 3548

Other (OTH) AF: 0.466 AC: 151 AN: 324

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

African (AFR) AF: 0.506 AC: 20922 AN: 41374

American (AMR) AF: 0.442 AC: 6742 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1755 AN: 3464

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5158

South Asian (SAS) AF: 0.431 AC: 2071 AN: 4810

European-Finnish (FIN) AF: 0.555 AC: 5847 AN: 10544

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.511 AC: 34706 AN: 67916

Other (OTH) AF: 0.463 AC: 975 AN: 2108

Alfa AF: 0.500 Hom.: 38623

Bravo AF: 0.487

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-0.51
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs340833;

hg19: chr3-3111458;