4-184629416-A-C
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_004346.4(CASP3):āc.690T>Gā(p.Leu230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,614,196 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 (ā ).
Frequency
Genomes: š 0.00035 ( 0 hom., cov: 33)
Exomes š: 0.000084 ( 1 hom. )
Consequence
CASP3
NM_004346.4 synonymous
NM_004346.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.299
Genes affected
CASP3 (HGNC:1504): (caspase 3) The protein encoded by this gene is a cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis. The encoded protein cleaves and inactivates poly(ADP-ribose) polymerase while it cleaves and activates sterol regulatory element binding proteins as well as caspases 6, 7, and 9. This protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 4-184629416-A-C is Benign according to our data. Variant chr4-184629416-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 799089.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.299 with no splicing effect.
BS2
High AC in GnomAd4 at 53 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP3 | NM_004346.4 | c.690T>G | p.Leu230= | synonymous_variant | 8/8 | ENST00000308394.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP3 | ENST00000308394.9 | c.690T>G | p.Leu230= | synonymous_variant | 8/8 | 1 | NM_004346.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251436Hom.: 1 AF XY: 0.000206 AC XY: 28AN XY: 135894
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GnomAD4 exome AF: 0.0000841 AC: 123AN: 1461866Hom.: 1 Cov.: 31 AF XY: 0.0000784 AC XY: 57AN XY: 727234
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GnomAD4 genome AF: 0.000348 AC: 53AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33AN XY: 74490
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at