chr12-98666243-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_181861.2(APAF1):c.1248G>A(p.Gln416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 0 hom. )
Consequence
APAF1
NM_181861.2 synonymous
NM_181861.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.360
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 12-98666243-G-A is Benign according to our data. Variant chr12-98666243-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3042926.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.36 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APAF1 | NM_181861.2 | c.1248G>A | p.Gln416= | synonymous_variant | 9/27 | ENST00000551964.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APAF1 | ENST00000551964.6 | c.1248G>A | p.Gln416= | synonymous_variant | 9/27 | 1 | NM_181861.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000572 AC: 87AN: 152172Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000143 AC: 36AN: 251372Hom.: 1 AF XY: 0.0000883 AC XY: 12AN XY: 135858
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GnomAD4 exome AF: 0.0000794 AC: 116AN: 1461670Hom.: 0 Cov.: 32 AF XY: 0.0000646 AC XY: 47AN XY: 727156
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GnomAD4 genome AF: 0.000591 AC: 90AN: 152290Hom.: 1 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
APAF1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at