chr3-3110075-C-T

Variant names:

• chr3-3110075-C-T
• rs2290608
• NM_175726.4:c.-276G>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.-276G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,152 control chromosomes in the GnomAD database, including 3,723 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 0.21 (3723 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: IL5RA NM_175726.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 21 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 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.-276G>A		5_prime_UTR	Exon 1 of 12	NP_783853.1
	IL5RA	NM_000564.5		c.-345G>A		5_prime_UTR	Exon 1 of 13	NP_000555.2
	IL5RA	NM_001243099.2		c.-276G>A		5_prime_UTR	Exon 1 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.-276G>A		5_prime_UTR	Exon 1 of 12	ENSP00000412209.2
	IL5RA	ENST00000383846.5	TSL:1	c.-276G>A		5_prime_UTR	Exon 1 of 10	ENSP00000373358.1
	IL5RA	ENST00000466722.1	TSL:4	n.291G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31865 AN: 152014 Hom.: 3728 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.0500 AC: 1 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

⚠️ 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) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 1 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 6

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.209 AC: 31849 AN: 152132 Hom.: 3723 Cov.: 32 AF XY: 0.211 AC XY: 15710 AN XY: 74358

African (AFR) AF: 0.104 AC: 4307 AN: 41520

American (AMR) AF: 0.219 AC: 3352 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3468

East Asian (EAS) AF: 0.193 AC: 996 AN: 5172

South Asian (SAS) AF: 0.176 AC: 847 AN: 4822

European-Finnish (FIN) AF: 0.285 AC: 3016 AN: 10566

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.256 AC: 17389 AN: 67994

Other (OTH) AF: 0.242 AC: 511 AN: 2112

Alfa AF: 0.241 Hom.: 7961

Bravo AF: 0.202

Asia WGS AF: 0.190 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.83
PhyloP100		-0.38
PromoterAI		0.022	Neutral
Mutation Taster		=300/0	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: rs2290608; hg19: chr3-3151759;