rs11713419

Variant names:

• chr3-3108583-A-G
• rs11713419
• NM_175726.4:c.-37T>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.-37T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,196 control chromosomes in the GnomAD database, including 2,994 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 0.19 (2993 hom., cov: 33)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: IL5RA NM_175726.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 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.-37T>C		5_prime_UTR	Exon 2 of 12	NP_783853.1
	IL5RA	NM_000564.5		c.-106T>C		5_prime_UTR	Exon 2 of 13	NP_000555.2
	IL5RA	NM_001243099.2		c.-37T>C		5_prime_UTR	Exon 2 of 11	NP_001230028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5RA	ENST00000446632.7	TSL:5 MANE Select	c.-37T>C		5_prime_UTR	Exon 2 of 12	ENSP00000412209.2
	IL5RA	ENST00000256452.7	TSL:1	c.-106T>C		5_prime_UTR	Exon 2 of 13	ENSP00000256452.3
	IL5RA	ENST00000311981.12	TSL:1	c.-106T>C		5_prime_UTR	Exon 2 of 11	ENSP00000309196.8

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28798 AN: 152058 Hom.: 2987 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.250 AC: 5 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 4 AN XY: 16

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.300 AC: 3 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0662318), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.189 AC: 28837 AN: 152176 Hom.: 2993 Cov.: 33 AF XY: 0.186 AC XY: 13857 AN XY: 74392

African (AFR) AF: 0.281 AC: 11659 AN: 41516

American (AMR) AF: 0.156 AC: 2377 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.159 AC: 825 AN: 5178

South Asian (SAS) AF: 0.0969 AC: 468 AN: 4828

European-Finnish (FIN) AF: 0.168 AC: 1781 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10859 AN: 67990

Other (OTH) AF: 0.165 AC: 347 AN: 2108

Alfa AF: 0.167 Hom.: 8459

Bravo AF: 0.192

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.42
PhyloP100		-0.96
Mutation Taster		=296/4	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: rs11713419; hg19: chr3-3150267;