chr1-15505981-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001229.5(CASP9):c.720+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00649 in 1,610,982 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0046 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0067 ( 59 hom. )
Consequence
CASP9
NM_001229.5 intron
NM_001229.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0410
Genes affected
CASP9 (HGNC:1511): (caspase 9) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 1-15505981-G-A is Benign according to our data. Variant chr1-15505981-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 777920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 706 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP9 | NM_001229.5 | c.720+9C>T | intron_variant | ENST00000333868.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP9 | ENST00000333868.10 | c.720+9C>T | intron_variant | 1 | NM_001229.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00464 AC: 706AN: 152218Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00357 AC: 896AN: 251206Hom.: 4 AF XY: 0.00367 AC XY: 498AN XY: 135830
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GnomAD4 exome AF: 0.00668 AC: 9749AN: 1458646Hom.: 59 Cov.: 29 AF XY: 0.00648 AC XY: 4705AN XY: 725924
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GnomAD4 genome ? AF: 0.00463 AC: 706AN: 152336Hom.: 4 Cov.: 33 AF XY: 0.00388 AC XY: 289AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CASP9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 09, 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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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