Genetic Variant IL5RA:c.-276G>A (chr3-3110075-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375

Publications

21 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4 link	c.-276G>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7 link	c.-276G>A		5_prime_UTR_variant	Exon 1 of 12	5	NM_175726.4	ENSP00000412209.2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31865

AN:

152014

Hom.:

3728

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.0714

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0714

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.209

AC:

31849

AN:

152132

Hom.:

3723

Cov.:

AF XY:

0.211

AC XY:

15710

AN XY:

74358

show subpopulations

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:

AN:

290

European-Non Finnish (NFE)

AF:

0.256

AC:

17389

AN:

67994

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1259

2518

3777

5036

6295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.7

(source)

DANN

Benign

0.83

PhyloP100

-0.38

PromoterAI

0.022

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over