Genetic Variant IL5:n.731A>G (chr5-132543190-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000462418.1(IL5):n.731A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,504,580 control chromosomes in the GnomAD database, including 206 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 0.010 ( 15 hom., cov: 32)

Exomes 𝑓: 0.015 ( 191 hom. )

Consequence

IL5
ENST00000462418.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.645

Publications

12 publications found

Variant links:

Genes affected

IL5 (HGNC:6016): (interleukin 5) This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31. [provided by RefSeq, Jul 2013]

IL5 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 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=-0.85).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0101 (1532/152324) while in subpopulation NFE AF = 0.0162 (1100/68018). AF 95% confidence interval is 0.0154. There are 15 homozygotes in GnomAd4. There are 736 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL5	NM_000879.3 link	c.145-64A>G	intron_variant	Intron 1 of 3	ENST00000231454.6	NP_000870.1	P05113
IL5	XM_005271988.5 link	c.211-64A>G	intron_variant	Intron 2 of 4		XP_005272045.1
IL5	XM_011543373.4 link	c.145-64A>G	intron_variant	Intron 3 of 5		XP_011541675.1	P05113
IL5	XM_047417148.1 link	c.43-64A>G	intron_variant	Intron 1 of 3		XP_047273104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5	ENST00000231454.6 link	c.145-64A>G		intron_variant	Intron 1 of 3	1	NM_000879.3	ENSP00000231454.1		P05113
ENSG00000283782	ENST00000638452.2 link	c.-168-16094T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1532

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.00765

GnomAD4 exome

AF:

0.0150

AC:

20241

AN:

1352256

Hom.:

191

Cov.:

AF XY:

0.0146

AC XY:

9874

AN XY:

678156

show subpopulations

African (AFR)

AF:

0.00281

AC:

AN:

30912

American (AMR)

AF:

0.00489

AC:

210

AN:

42914

Ashkenazi Jewish (ASJ)

AF:

0.00728

AC:

184

AN:

25282

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39094

South Asian (SAS)

AF:

0.00107

AC:

AN:

82054

European-Finnish (FIN)

AF:

0.0107

AC:

569

AN:

53276

Middle Eastern (MID)

AF:

0.00306

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.0181

AC:

18422

AN:

1016366

Other (OTH)

AF:

0.0117

AC:

663

AN:

56806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

999

1998

2998

3997

4996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

664

1328

1992

2656

3320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0101

AC:

1532

AN:

152324

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

736

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41576

American (AMR)

AF:

0.00882

AC:

135

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00664

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0122

AC:

130

AN:

10618

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0162

AC:

1100

AN:

68018

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0152

Hom.:

Bravo

AF:

0.00935

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.061

(source)

DANN

Benign

0.73

PhyloP100

-0.65

PromoterAI

-0.0086

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over