NM_175726.4:c.994+4131T>C

Variant names:

• chr3-3088093-A-G
• rs10510252
• NM_175726.4:c.994+4131T>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.994+4131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 152,304 control chromosomes in the GnomAD database, including 62 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 0.026 (62 hom., cov: 32)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.994+4131T>C		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+4131T>C		intron_variant	Intron 9 of 11	5	NM_175726.4	ENSP00000412209.2
IL5RA	ENST00000256452.7	c.994+4131T>C		intron_variant	Intron 10 of 12	1		ENSP00000256452.3
IL5RA	ENST00000438560.5	c.994+4131T>C		intron_variant	Intron 9 of 10	2		ENSP00000390753.1
IL5RA	ENST00000418488.6	c.709+9777T>C		intron_variant	Intron 8 of 10	5		ENSP00000388858.2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3959 AN: 152186 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0260 AC: 3960 AN: 152304 Hom.: 62 Cov.: 32 AF XY: 0.0282 AC XY: 2097 AN XY: 74468

African (AFR) AF: 0.00483 AC: 201 AN: 41588

American (AMR) AF: 0.0551 AC: 842 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3470

East Asian (EAS) AF: 0.0527 AC: 273 AN: 5182

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4826

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1802 AN: 68018

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0254 Hom.: 118

Bravo AF: 0.0247

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.46
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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: rs10510252; hg19: chr3-3129777;