Variant chr3-3098154-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_175726.4(IL5RA):c.504G>C(p.Gln168His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IL5RA
NM_175726.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.241

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL5RA	NM_175726.4 linkuse as main transcript	c.504G>C	p.Gln168His	missense_variant	6/12	ENST00000446632.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL5RA	ENST00000446632.7 linkuse as main transcript	c.504G>C	p.Gln168His	missense_variant	6/12	5	NM_175726.4	P2	Q01344-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.504G>C (p.Q168H) alteration is located in exon 1 (coding exon 1) of the IL5RA gene. This alteration results from a G to C substitution at nucleotide position 504, causing the glutamine (Q) at amino acid position 168 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.73

D;D;.;D;.;.;.;.;D

Eigen

Benign

-0.014

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.68

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

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.4

.;M;M;M;M;M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.48

Sift

Benign

0.040

D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.045

D;D;D;D;D;D;D;D;.

Polyphen

0.51

P;P;.;P;B;B;B;B;.

Vest4

0.20

MutPred

0.87

Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);Loss of catalytic residue at Q168 (P = 0.2013);

MVP

0.91

MPC

0.084

ClinPred

0.89

GERP RS

3.1

Varity_R

0.42

gMVP

0.69

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over