chr14-23375867-G-A
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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
NM_022789.4 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 2.64
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]
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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 | c.473G>A | p.Arg158His | missense_variant | 3/3 | ENST00000397242.3 | NP_758525.1 | |
IL25 | NM_022789.4 | 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 | c.473G>A | p.Arg158His | missense_variant | 3/3 | 1 | NM_172314.2 | ENSP00000380417 | P2 | |
IL25 | ENST00000329715.2 | c.521G>A | p.Arg174His | missense_variant | 2/2 | 1 | ENSP00000328111 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00568 AC: 865AN: 152240Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00571 AC: 1432AN: 250892Hom.: 6 AF XY: 0.00596 AC XY: 808AN XY: 135548
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GnomAD4 exome AF: 0.00791 AC: 11565AN: 1461628Hom.: 72 Cov.: 32 AF XY: 0.00789 AC XY: 5740AN XY: 727080
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GnomAD4 genome AF: 0.00568 AC: 865AN: 152358Hom.: 7 Cov.: 33 AF XY: 0.00540 AC XY: 402AN XY: 74506
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.48
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at