rs580253
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_001257118.3(CASP1):c.766C>T(p.Leu256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,612,946 control chromosomes in the GnomAD database, including 23,608 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 0.15 ( 2029 hom., cov: 32)
Exomes 𝑓: 0.16 ( 21579 hom. )
Consequence
CASP1
NM_001257118.3 synonymous
NM_001257118.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.744
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP7
?
Synonymous conserved (PhyloP=0.744 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP1 | NM_001257118.3 | c.766C>T | p.Leu256= | synonymous_variant | 6/9 | ENST00000533400.6 | |
LOC124902742 | XR_007062869.1 | n.41-1586G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP1 | ENST00000533400.6 | c.766C>T | p.Leu256= | synonymous_variant | 6/9 | 1 | NM_001257118.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.152 AC: 23157AN: 151920Hom.: 2025 Cov.: 32
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GnomAD3 exomes AF: 0.172 AC: 43261AN: 251230Hom.: 4715 AF XY: 0.165 AC XY: 22434AN XY: 135776
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GnomAD4 exome AF: 0.165 AC: 240476AN: 1460908Hom.: 21579 Cov.: 33 AF XY: 0.162 AC XY: 117585AN XY: 726834
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GnomAD4 genome ? AF: 0.152 AC: 23183AN: 152038Hom.: 2029 Cov.: 32 AF XY: 0.155 AC XY: 11521AN XY: 74318
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Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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