3-3098273-T-A

Variant names:

• chr3-3098273-T-A
• rs2290610
• NM_175726.4:c.385A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175726.4(IL5RA):​c.385A>T​(p.Ile129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I129T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL5RA NM_175726.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 42 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18880343).

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.385A>T	p.Ile129Phe	missense	Exon 6 of 12	NP_783853.1
	IL5RA	NM_000564.5		c.385A>T	p.Ile129Phe	missense	Exon 7 of 13	NP_000555.2
	IL5RA	NM_001243099.2		c.385A>T	p.Ile129Phe	missense	Exon 6 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.385A>T	p.Ile129Phe	missense	Exon 6 of 12	ENSP00000412209.2
	IL5RA	ENST00000256452.7	TSL:1	c.385A>T	p.Ile129Phe	missense	Exon 7 of 13	ENSP00000256452.3
	IL5RA	ENST00000311981.12	TSL:1	c.385A>T	p.Ile129Phe	missense	Exon 7 of 11	ENSP00000309196.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.30
DANN	Benign	0.65
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.063	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.51
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.84	P
Vest4		0.44
MutPred		0.33		Loss of glycosylation at S128 (P = 0.0606)
MVP		0.42
MPC		0.095
ClinPred		0.78	D
GERP RS		-4.2
Varity_R		0.33
gMVP		0.61
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2290610; hg19: chr3-3139957;