Variant 14-23375770-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022789.4(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
NM_022789.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.869

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
IL25	NM_172314.2 linkuse as main transcript	c.376C>T	p.Arg126Trp	missense_variant	3/3	ENST00000397242.3	NP_758525.1
IL25	NM_022789.4 linkuse as main transcript	c.424C>T	p.Arg142Trp	missense_variant	2/2		NP_073626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL25	ENST00000397242.3 linkuse as main transcript	c.376C>T	p.Arg126Trp	missense_variant	3/3	1	NM_172314.2	ENSP00000380417	P2	Q9H293-2
IL25	ENST00000329715.2 linkuse as main transcript	c.424C>T	p.Arg142Trp	missense_variant	2/2	1		ENSP00000328111	A2	Q9H293-1

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

GnomAD3 exomes

AF:

0.00644

AC:

1618

AN:

251366

Hom.:

AF XY:

0.00644

AC XY:

875

AN XY:

135878

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 SAS exome

AF:

0.00216

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

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00416

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00879

GnomAD4 genome

AF:

0.00632

AC:

962

AN:

152198

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00859

Hom.:

809

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -

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

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

MutationTaster

Benign

0.72

D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over