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

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

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

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14-23375770-C-A

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