Variant 3-3098273-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175726.4(IL5RA):c.385A>G(p.Ile129Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,612,150 control chromosomes in the GnomAD database, including 112,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 10557 hom., cov: 32)

Exomes 𝑓: 0.37 ( 101710 hom. )

Consequence

IL5RA
NM_175726.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Variant links:

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]

IL5RA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.54885E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL5RA	NM_175726.4 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	6/12	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	6/12	5	NM_175726.4	ENSP00000412209	P2	Q01344-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55946

AN:

151920

Hom.:

10549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.386

GnomAD3 exomes

AF:

0.384

AC:

96516

AN:

251350

Hom.:

19613

AF XY:

0.392

AC XY:

53185

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.391

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.219

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.368

AC:

536899

AN:

1460112

Hom.:

101710

Cov.:

AF XY:

0.373

AC XY:

270857

AN XY:

726530

show subpopulations

Gnomad4 AFR exome

AF:

0.381

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.385

GnomAD4 genome

AF:

0.368

AC:

55985

AN:

152038

Hom.:

10557

Cov.:

AF XY:

0.367

AC XY:

27290

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.369

Hom.:

23742

Bravo

AF:

0.376

TwinsUK

AF:

0.356

AC:

1320

ALSPAC

AF:

0.365

AC:

1406

ESP6500AA

AF:

0.392

AC:

1726

ESP6500EA

AF:

0.367

AC:

3152

ExAC

AF:

0.388

AC:

47142

Asia WGS

AF:

0.493

AC:

1713

AN:

3478

EpiCase

AF:

0.371

EpiControl

AF:

0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0020

DANN

Benign

0.65

DEOGEN2

Benign

0.23

T;T;.;T;.;.;.;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.49

T;.;T;T;.;T;.;T;T

MetaRNN

Benign

0.000015

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.14

.;N;N;N;N;N;N;N;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.020

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.050

Sift

Benign

1.0

T;T;T;T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;.

Polyphen

0.0010

B;B;.;B;B;B;B;B;.

Vest4

0.036

MPC

0.029

ClinPred

0.0025

GERP RS

-4.2

Varity_R

0.038

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over