NM_175726.4:c.994+3687T>A

Variant names:

• chr3-3088537-A-T
• rs334809
• NM_175726.4:c.994+3687T>A

Variant summary

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

The NM_175726.4(IL5RA):​c.994+3687T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,190 control chromosomes in the GnomAD database, including 42,427 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 0.74 (42427 hom., cov: 33)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 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.994+3687T>A		intron	N/A	NP_783853.1	Q01344-1
	IL5RA	NM_000564.5		c.994+3687T>A		intron	N/A	NP_000555.2
	IL5RA	NM_001243099.2		c.994+3687T>A		intron	N/A	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.994+3687T>A		intron	N/A	ENSP00000412209.2	Q01344-1
	IL5RA	ENST00000256452.7	TSL:1	c.994+3687T>A		intron	N/A	ENSP00000256452.3	Q01344-1
	IL5RA	ENST00000438560.5	TSL:2	c.994+3687T>A		intron	N/A	ENSP00000390753.1	Q01344-4

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111905 AN: 152072 Hom.: 42349 Cov.: 33

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.736 AC: 112047 AN: 152190 Hom.: 42427 Cov.: 33 AF XY: 0.731 AC XY: 54381 AN XY: 74402

African (AFR) AF: 0.934 AC: 38833 AN: 41562

American (AMR) AF: 0.714 AC: 10917 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3106 AN: 5172

South Asian (SAS) AF: 0.646 AC: 3118 AN: 4828

European-Finnish (FIN) AF: 0.622 AC: 6573 AN: 10574

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45015 AN: 67974

Other (OTH) AF: 0.706 AC: 1491 AN: 2112

Alfa AF: 0.694 Hom.: 4414

Bravo AF: 0.750

Asia WGS AF: 0.663 AC: 2307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.52
PhyloP100		-0.20
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: rs334809; hg19: chr3-3130221;