11-72000018-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001039660.2(IL18BP):c.28+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,738 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
IL18BP
NM_001039660.2 splice_donor_region, intron
NM_001039660.2 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001264
2
Clinical Significance
Conservation
PhyloP100: -1.95
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL18BP | NM_001039660.2 | c.28+6C>T | splice_donor_region_variant, intron_variant | ENST00000393703.9 | NP_001034749.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL18BP | ENST00000393703.9 | c.28+6C>T | splice_donor_region_variant, intron_variant | 3 | NM_001039660.2 | ENSP00000377306 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248432Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134824
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461514Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 727070
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2024 | This sequence change falls in intron 1 of the IL18BP gene. It does not directly change the encoded amino acid sequence of the IL18BP protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs756889830, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with IL18BP-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at