3-3087948-T-C

Variant names:

• chr3-3087948-T-C
• rs3804797
• NM_175726.4:c.994+4276A>G

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+4276A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,090 control chromosomes in the GnomAD database, including 2,117 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 0.15 (2117 hom., cov: 32)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 4 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.994+4276A>G		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.994+4276A>G		intron_variant	Intron 9 of 11	5	NM_175726.4	ENSP00000412209.2
IL5RA	ENST00000256452.7	c.994+4276A>G		intron_variant	Intron 10 of 12	1		ENSP00000256452.3
IL5RA	ENST00000438560.5	c.994+4276A>G		intron_variant	Intron 9 of 10	2		ENSP00000390753.1
IL5RA	ENST00000418488.6	c.709+9922A>G		intron_variant	Intron 8 of 10	5		ENSP00000388858.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23438 AN: 151972 Hom.: 2122 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.154 AC: 23446 AN: 152090 Hom.: 2117 Cov.: 32 AF XY: 0.159 AC XY: 11793 AN XY: 74350

African (AFR) AF: 0.120 AC: 4983 AN: 41476

American (AMR) AF: 0.151 AC: 2309 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 650 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1936 AN: 5160

South Asian (SAS) AF: 0.351 AC: 1687 AN: 4808

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10584

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10178 AN: 67994

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.148 Hom.: 3488

Bravo AF: 0.151

Asia WGS AF: 0.288 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		0.36
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: rs3804797; hg19: chr3-3129632;