NM_175726.4:c.995-7130C>A

Variant names:

• chr3-3083757-G-T
• rs17026370
• NM_175726.4:c.995-7130C>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.995-7130C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 152,242 control chromosomes in the GnomAD database, including 1,442 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 0.092 (1442 hom., cov: 33)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 2 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 = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.995-7130C>A		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.995-7130C>A		intron_variant	Intron 9 of 11	5	NM_175726.4	ENSP00000412209.2
IL5RA	ENST00000256452.7	c.995-7130C>A		intron_variant	Intron 10 of 12	1		ENSP00000256452.3
IL5RA	ENST00000438560.5	c.995-7130C>A		intron_variant	Intron 9 of 10	2		ENSP00000390753.1
IL5RA	ENST00000418488.6	c.710-7130C>A		intron_variant	Intron 8 of 10	5		ENSP00000388858.2

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13891 AN: 152124 Hom.: 1431 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0916 AC: 13945 AN: 152242 Hom.: 1442 Cov.: 33 AF XY: 0.0907 AC XY: 6752 AN XY: 74424

African (AFR) AF: 0.255 AC: 10605 AN: 41522

American (AMR) AF: 0.0432 AC: 660 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 222 AN: 3472

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5174

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4826

European-Finnish (FIN) AF: 0.0394 AC: 418 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0224 AC: 1521 AN: 68022

Other (OTH) AF: 0.0860 AC: 182 AN: 2116

Alfa AF: 0.0501 Hom.: 421

Bravo AF: 0.0983

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.082
DANN	Benign	0.34
PhyloP100		-1.3
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: rs17026370; hg19: chr3-3125441;