Genetic Variant IL25:p.Arg142Arg (chr14-23375770-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The ENST00000329715.2(IL25):c.424C>A(p.Arg142Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,614,028 control chromosomes in the GnomAD database, including 41,201 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 0.25 ( 5461 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35740 hom. )

Consequence

IL25
ENST00000329715.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.869

Publications

23 publications found

Variant links:

Genes affected

IL25 (HGNC:13765): (interleukin 25) The protein encoded by this gene is a cytokine that shares sequence similarity with interleukin 17. This cytokine can induce NF-kappaB activation, and stimulate the production of interleukin 8. Both this cytokine and interleukin 17B are ligands for the cytokine receptor IL17BR. Studies of a similar gene in mice suggest that this cytokine may be a pro-inflammatory cytokine favoring the Th2-type immune response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

IL25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP7

Synonymous conserved (PhyloP=0.869 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL25	NM_022789.4 link	c.424C>A	p.Arg142Arg	synonymous_variant	Exon 2 of 2		NP_073626.1	Q9H293-1
IL25	NM_172314.2 link	c.376C>A	p.Arg126Arg	synonymous_variant	Exon 3 of 3		NP_758525.1	Q9H293-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL25	ENST00000329715.2 link	c.424C>A	p.Arg142Arg	synonymous_variant	Exon 2 of 2	1		ENSP00000328111.2		Q9H293-1
IL25	ENST00000397242.3 link	c.376C>A	p.Arg126Arg	synonymous_variant	Exon 3 of 3	1		ENSP00000380417.2		Q9H293-2

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38555

AN:

152038

Hom.:

5444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.210

AC:

52860

AN:

251366

AF XY:

0.209

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.217

AC:

317570

AN:

1461874

Hom.:

35740

Cov.:

AF XY:

0.216

AC XY:

156888

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.383

AC:

12813

AN:

33480

American (AMR)

AF:

0.152

AC:

6779

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

5032

AN:

26136

East Asian (EAS)

AF:

0.255

AC:

10116

AN:

39700

South Asian (SAS)

AF:

0.203

AC:

17515

AN:

86258

European-Finnish (FIN)

AF:

0.178

AC:

9488

AN:

53418

Middle Eastern (MID)

AF:

0.206

AC:

1188

AN:

5768

European-Non Finnish (NFE)

AF:

0.217

AC:

240757

AN:

1111996

Other (OTH)

AF:

0.230

AC:

13882

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16507

33014

49522

66029

82536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8534

17068

25602

34136

42670

<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:

0.254

AC:

38607

AN:

152154

Hom.:

5461

Cov.:

AF XY:

0.250

AC XY:

18602

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.376

AC:

15593

AN:

41480

American (AMR)

AF:

0.197

AC:

3015

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

663

AN:

3466

East Asian (EAS)

AF:

0.255

AC:

1319

AN:

5174

South Asian (SAS)

AF:

0.204

AC:

984

AN:

4830

European-Finnish (FIN)

AF:

0.189

AC:

2008

AN:

10614

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.209

AC:

14233

AN:

67988

Other (OTH)

AF:

0.273

AC:

576

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1464

2928

4391

5855

7319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.190

Hom.:

2953

Bravo

AF:

0.262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

9.6

(source)

DANN

Benign

0.74

PhyloP100

0.87

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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