Variant 14-23375867-G-A 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.521G>A(p.Arg174His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,613,986 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 72 hom. )

Consequence

IL25
NM_022789.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.64

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=0.011588514).

BP6

Variant 14-23375867-G-A is Benign according to our data. Variant chr14-23375867-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 791055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL25	NM_172314.2 linkuse as main transcript	c.473G>A	p.Arg158His	missense_variant	3/3	ENST00000397242.3	NP_758525.1
IL25	NM_022789.4 linkuse as main transcript	c.521G>A	p.Arg174His	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.473G>A	p.Arg158His	missense_variant	3/3	1	NM_172314.2	ENSP00000380417	P2	Q9H293-2
IL25	ENST00000329715.2 linkuse as main transcript	c.521G>A	p.Arg174His	missense_variant	2/2	1		ENSP00000328111	A2	Q9H293-1

Frequencies

GnomAD3 genomes

AF:

0.00568

AC:

865

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00842

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00571

AC:

1432

AN:

250892

Hom.:

AF XY:

0.00596

AC XY:

808

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00532

Gnomad ASJ exome

AF:

0.00825

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00340

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00851

Gnomad OTH exome

AF:

0.00572

GnomAD4 exome

AF:

0.00791

AC:

11565

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00789

AC XY:

5740

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00530

Gnomad4 ASJ exome

AF:

0.00865

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00368

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00916

Gnomad4 OTH exome

AF:

0.00667

GnomAD4 genome

AF:

0.00568

AC:

865

AN:

152358

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00842

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00791

Hom.:

Bravo

AF:

0.00559

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00547

AC:

664

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.70

.;D

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

0.83

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.46

MVP

0.74

MPC

0.48

ClinPred

0.029

GERP RS

4.6

Varity_R

0.25

gMVP

0.46

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