chr14-23375743-C-G

Variant summary

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

The NM_022789.4(IL25):ā€‹c.397C>Gā€‹(p.Leu133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Consequence

IL25
NM_022789.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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=0.33286896).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL25NM_172314.2 linkuse as main transcriptc.349C>G p.Leu117Val missense_variant 3/3 ENST00000397242.3 NP_758525.1
IL25NM_022789.4 linkuse as main transcriptc.397C>G p.Leu133Val 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.349C>G p.Leu117Val missense_variant 3/31 NM_172314.2 ENSP00000380417 P2Q9H293-2
IL25ENST00000329715.2 linkuse as main transcriptc.397C>G p.Leu133Val missense_variant 2/21 ENSP00000328111 A2Q9H293-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
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
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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
Bravo
AF:
0.00000756

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 GeneticsOct 03, 2022The c.397C>G (p.L133V) 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 397, causing the leucine (L) at amino acid position 133 to be replaced by a valine (V). 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
0.30
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.69
T;T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.4
.;L
MutationTaster
Benign
0.64
N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.18
Sift
Benign
0.17
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.22
MutPred
0.48
.;Gain of sheet (P = 0.1539);
MVP
0.61
MPC
0.29
ClinPred
0.85
D
GERP RS
4.5
Varity_R
0.16
gMVP
0.21

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: rs914496697; hg19: chr14-23844952; API