14-23375852-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022789.4(IL25):ā€‹c.506T>Cā€‹(p.Val169Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00021 ( 0 hom., cov: 33)
Exomes š‘“: 0.000022 ( 0 hom. )

Consequence

IL25
NM_022789.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28541774).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL25NM_172314.2 linkuse as main transcriptc.458T>C p.Val153Ala missense_variant 3/3 ENST00000397242.3 NP_758525.1
IL25NM_022789.4 linkuse as main transcriptc.506T>C p.Val169Ala missense_variant 2/2 NP_073626.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL25ENST00000397242.3 linkuse as main transcriptc.458T>C p.Val153Ala missense_variant 3/31 NM_172314.2 ENSP00000380417 P2Q9H293-2
IL25ENST00000329715.2 linkuse as main transcriptc.506T>C p.Val169Ala missense_variant 2/21 ENSP00000328111 A2Q9H293-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000772
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251318
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000687
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.000772
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 27, 2022The c.506T>C (p.V169A) alteration is located in exon 2 (coding exon 2) of the IL25 gene. This alteration results from a T to C substitution at nucleotide position 506, causing the valine (V) at amino acid position 169 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
.;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.7
.;L
MutationTaster
Benign
0.80
N;N
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.21
Sift
Benign
0.11
T;T
Sift4G
Uncertain
0.038
D;D
Polyphen
0.99
D;P
Vest4
0.53
MVP
0.61
MPC
0.42
ClinPred
0.12
T
GERP RS
4.6
Varity_R
0.087
gMVP
0.50

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.

Other links and lift over

dbSNP: rs149802556; hg19: chr14-23845061; API