rs2278361
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_181861.2(APAF1):c.329-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,563,344 control chromosomes in the GnomAD database, including 32,518 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.19 ( 2967 hom., cov: 33)
Exomes 𝑓: 0.20 ( 29551 hom. )
Consequence
APAF1
NM_181861.2 intron
NM_181861.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.246
Genes affected
APAF1 (HGNC:576): (apoptotic peptidase activating factor 1) This gene encodes a cytoplasmic protein that initiates apoptosis. This protein contains several copies of the WD-40 domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APAF1 | NM_181861.2 | c.329-58A>G | intron_variant | ENST00000551964.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APAF1 | ENST00000551964.6 | c.329-58A>G | intron_variant | 1 | NM_181861.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.192 AC: 29172AN: 152050Hom.: 2962 Cov.: 33
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GnomAD4 exome AF: 0.201 AC: 283360AN: 1411176Hom.: 29551 AF XY: 0.197 AC XY: 139040AN XY: 704632
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GnomAD4 genome ? AF: 0.192 AC: 29191AN: 152168Hom.: 2967 Cov.: 33 AF XY: 0.191 AC XY: 14223AN XY: 74386
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at