14-23375776-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022789.4(IL25):ā€‹c.430C>Gā€‹(p.Pro144Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 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‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

IL25
NM_022789.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL25NM_172314.2 linkuse as main transcriptc.382C>G p.Pro128Ala missense_variant 3/3 ENST00000397242.3 NP_758525.1
IL25NM_022789.4 linkuse as main transcriptc.430C>G p.Pro144Ala 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.382C>G p.Pro128Ala missense_variant 3/31 NM_172314.2 ENSP00000380417 P2Q9H293-2
IL25ENST00000329715.2 linkuse as main transcriptc.430C>G p.Pro144Ala missense_variant 2/21 ENSP00000328111 A2Q9H293-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152250
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000224
Hom.:
0

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 31, 2022The c.430C>G (p.P144A) alteration is located in exon 2 (coding exon 2) of the IL25 gene. This alteration results from a C to G substitution at nucleotide position 430, causing the proline (P) at amino acid position 144 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
Benign
0.095
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.61
.;D
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.70
D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.9
.;L
MutationTaster
Benign
0.77
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-5.6
D;D
REVEL
Benign
0.21
Sift
Benign
0.075
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.88
P;D
Vest4
0.30
MutPred
0.86
.;Gain of MoRF binding (P = 0.059);
MVP
0.73
MPC
0.33
ClinPred
0.95
D
GERP RS
4.5
Varity_R
0.16
gMVP
0.25

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: rs1359119715; hg19: chr14-23844985; API