3-3076016-A-G

Variant names:

• chr3-3076016-A-G
• rs3792424
• NM_175726.4:c.1091+515T>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.1091+515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,202 control chromosomes in the GnomAD database, including 1,190 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 0.11 (1190 hom., cov: 32)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	NM_175726.4	MANE Select	c.1091+515T>C		intron	N/A	NP_783853.1
	IL5RA	NM_000564.5		c.1091+515T>C		intron	N/A	NP_000555.2
	IL5RA	NM_001243099.2		c.1091+515T>C		intron	N/A	NP_001230028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	ENST00000446632.7	TSL:5 MANE Select	c.1091+515T>C		intron	N/A	ENSP00000412209.2
	IL5RA	ENST00000256452.7	TSL:1	c.1091+515T>C		intron	N/A	ENSP00000256452.3
	IL5RA	ENST00000438560.5	TSL:2	c.1091+515T>C		intron	N/A	ENSP00000390753.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16580 AN: 152084 Hom.: 1188 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.0999

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.109 AC: 16598 AN: 152202 Hom.: 1190 Cov.: 32 AF XY: 0.106 AC XY: 7869 AN XY: 74426

African (AFR) AF: 0.205 AC: 8511 AN: 41486

American (AMR) AF: 0.0680 AC: 1040 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 347 AN: 3472

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5180

South Asian (SAS) AF: 0.0928 AC: 447 AN: 4818

European-Finnish (FIN) AF: 0.0630 AC: 669 AN: 10622

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0761 AC: 5176 AN: 68012

Other (OTH) AF: 0.104 AC: 221 AN: 2116

Alfa AF: 0.0881 Hom.: 1322

Bravo AF: 0.113

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.55
PhyloP100		-0.52
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: rs3792424; hg19: chr3-3117700;