14-24306417-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001393339.1(CIDEB):c.293G>A(p.Cys98Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,136 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
CIDEB
NM_001393339.1 missense
NM_001393339.1 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 0.771
Genes affected
CIDEB (HGNC:1977): (cell death inducing DFFA like effector b) Enables identical protein binding activity. Involved in activation of cysteine-type endopeptidase activity; positive regulation of cell death; and positive regulation of release of cytochrome c from mitochondria. Acts upstream of or within apoptotic process. Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]
LTB4R2 (HGNC:19260): (leukotriene B4 receptor 2) Predicted to enable G protein-coupled peptide receptor activity and leukotriene B4 receptor activity. Predicted to be involved in inflammatory response and neuropeptide signaling pathway. Predicted to act upstream of or within keratinocyte migration and signal transduction. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|---|
CIDEB | NM_001393339.1 | c.293G>A | p.Cys98Tyr | missense_variant | 3/5 | ENST00000554411.6 | NP_001380268.1 | |
NOP9 | NM_174913.3 | c.*1322C>T | 3_prime_UTR_variant | 10/10 | ENST00000267425.8 | NP_777573.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CIDEB | ENST00000554411.6 | c.293G>A | p.Cys98Tyr | missense_variant | 3/5 | 1 | NM_001393339.1 | ENSP00000451089 | P1 | |
NOP9 | ENST00000267425.8 | c.*1322C>T | 3_prime_UTR_variant | 10/10 | 1 | NM_174913.3 | ENSP00000267425 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251494Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
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GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727248
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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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 submitter | clinical testing | Ambry Genetics | May 20, 2024 | The c.293G>A (p.C98Y) alteration is located in exon 5 (coding exon 3) of the CIDEB gene. This alteration results from a G to A substitution at nucleotide position 293, causing the cysteine (C) at amino acid position 98 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;N;N;N;N;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MutPred
Gain of phosphorylation at C98 (P = 0.0085);Gain of phosphorylation at C98 (P = 0.0085);Gain of phosphorylation at C98 (P = 0.0085);
MVP
MPC
0.45
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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