11-72000363-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001039660.2(IL18BP):āc.41T>Cā(p.Leu14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,796 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 ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
IL18BP
NM_001039660.2 missense
NM_001039660.2 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.683
Genes affected
IL18BP (HGNC:5987): (interleukin 18 binding protein) The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]
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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 |
---|---|---|---|---|---|---|---|---|
IL18BP | NM_001039660.2 | c.41T>C | p.Leu14Ser | missense_variant | 3/6 | ENST00000393703.9 | NP_001034749.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL18BP | ENST00000393703.9 | c.41T>C | p.Leu14Ser | missense_variant | 3/6 | 3 | NM_001039660.2 | ENSP00000377306 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248698Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135020
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461624Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727126
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2024 | The c.41T>C (p.L14S) alteration is located in exon 2 (coding exon 2) of the IL18BP gene. This alteration results from a T to C substitution at nucleotide position 41, causing the leucine (L) at amino acid position 14 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with IL18BP-related conditions. This variant is present in population databases (rs748178291, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 14 of the IL18BP protein (p.Leu14Ser). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;.;.;T;T;.;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;L;.;L;L;L
MutationTaster
Benign
N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;.;N;N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;.;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;.;D;D;D;D
Vest4
MutPred
Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);Loss of catalytic residue at L14 (P = 0.0062);
MVP
MPC
0.19
ClinPred
T
GERP RS
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gMVP
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