14-23375861-G-A

Variant summary

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

The NM_022789.4(IL25):​c.515G>A​(p.Arg172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

IL25
NM_022789.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90
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=0.39966783).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL25NM_172314.2 linkuse as main transcriptc.467G>A p.Arg156Gln missense_variant 3/3 ENST00000397242.3 NP_758525.1
IL25NM_022789.4 linkuse as main transcriptc.515G>A p.Arg172Gln 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.467G>A p.Arg156Gln missense_variant 3/31 NM_172314.2 ENSP00000380417 P2Q9H293-2
IL25ENST00000329715.2 linkuse as main transcriptc.515G>A p.Arg172Gln missense_variant 2/21 ENSP00000328111 A2Q9H293-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
251056
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135646
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461732
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsMay 25, 2022The c.515G>A (p.R172Q) alteration is located in exon 2 (coding exon 2) of the IL25 gene. This alteration results from a G to A substitution at nucleotide position 515, causing the arginine (R) at amino acid position 172 to be replaced by a glutamine (Q). 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
Benign
0.31
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.25
.;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.40
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.4
.;M
MutationTaster
Benign
0.92
N;N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.93
N;N
REVEL
Benign
0.24
Sift
Benign
0.28
T;T
Sift4G
Benign
0.26
T;T
Polyphen
1.0
D;D
Vest4
0.38
MVP
0.75
MPC
0.50
ClinPred
0.20
T
GERP RS
3.6
Varity_R
0.090
gMVP
0.51

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: rs145694193; hg19: chr14-23845070; COSMIC: COSV59305428; COSMIC: COSV59305428; API