Genetic Variant ENST00000329715.2:c.424C>T (chr14-23375770-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000329715.2(IL25):c.424C>T(p.Arg142Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,614,086 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 5 hom., cov: 33)

Exomes 𝑓: 0.010 ( 98 hom. )

Consequence

IL25
ENST00000329715.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015012741).

BP6

Variant 14-23375770-C-T is Benign according to our data. Variant chr14-23375770-C-T is described in ClinVar as Benign. ClinVar VariationId is 775101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL25	NM_022789.4 link	c.424C>T	p.Arg142Trp	missense_variant	Exon 2 of 2		NP_073626.1	Q9H293-1
IL25	NM_172314.2 link	c.376C>T	p.Arg126Trp	missense_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>T	p.Arg142Trp	missense_variant	Exon 2 of 2	1		ENSP00000328111.2		Q9H293-1
IL25	ENST00000397242.3 link	c.376C>T	p.Arg126Trp	missense_variant	Exon 3 of 3	1		ENSP00000380417.2		Q9H293-2

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

962

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00644

AC:

1618

AN:

251366

AF XY:

0.00644

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00986

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.0104

AC:

15229

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

7341

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

33480

American (AMR)

AF:

0.00416

AC:

186

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

446

AN:

26136

East Asian (EAS)

AF:

0.000529

AC:

AN:

39700

South Asian (SAS)

AF:

0.00278

AC:

240

AN:

86258

European-Finnish (FIN)

AF:

0.00217

AC:

116

AN:

53418

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0122

AC:

13621

AN:

1112010

Other (OTH)

AF:

0.00879

AC:

531

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

952

1903

2855

3806

4758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.00632

AC:

962

AN:

152198

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

41506

American (AMR)

AF:

0.00399

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0106

AC:

720

AN:

67994

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

106

158

211

264

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:

0.0432

Hom.:

2953

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0138

AC:

ExAC

AF:

0.00592

AC:

719

EpiCase

AF:

0.00981

EpiControl

AF:

0.0101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

.;D

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.015

T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Pathogenic

3.2

.;M

PhyloP100

0.87

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.73

MVP

0.77

MPC

0.48

ClinPred

0.055

GERP RS

3.6

Varity_R

0.64

gMVP

0.68

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over