11-105031189-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001257118.3(CASP1):c.429G>A(p.Arg143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,611,706 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 32 hom. )
Consequence
CASP1
NM_001257118.3 synonymous
NM_001257118.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.990
Genes affected
CASP1 (HGNC:1499): (caspase 1) This gene encodes a protein which is 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 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]
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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=-0.85).
BP6
Variant 11-105031189-C-T is Benign according to our data. Variant chr11-105031189-C-T is described in ClinVar as [Benign]. Clinvar id is 709976.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.99 with no splicing effect.
BS2
High AC in GnomAd4 at 720 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP1 | NM_001257118.3 | c.429G>A | p.Arg143= | synonymous_variant | 4/9 | ENST00000533400.6 | |
LOC124902742 | XR_007062869.1 | n.41-158C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP1 | ENST00000533400.6 | c.429G>A | p.Arg143= | synonymous_variant | 4/9 | 1 | NM_001257118.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00473 AC: 720AN: 152146Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00478 AC: 1199AN: 250870Hom.: 12 AF XY: 0.00464 AC XY: 629AN XY: 135588
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GnomAD4 exome AF: 0.00436 AC: 6358AN: 1459442Hom.: 32 Cov.: 29 AF XY: 0.00440 AC XY: 3192AN XY: 726166
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GnomAD4 genome AF: 0.00473 AC: 720AN: 152264Hom.: 4 Cov.: 32 AF XY: 0.00489 AC XY: 364AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2018 | - - |
Computational scores
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Benign
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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