rs776532518
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_000719.7(CACNA1C):c.456C>T(p.Ser152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
CACNA1C
NM_000719.7 synonymous
NM_000719.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.89
Genes affected
CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 12-2120409-C-T is Benign according to our data. Variant chr12-2120409-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456971.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.456C>T | p.Ser152= | synonymous_variant | 3/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.456C>T | p.Ser152= | synonymous_variant | 3/47 | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.456C>T | p.Ser152= | synonymous_variant | 3/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.456C>T | p.Ser152= | synonymous_variant | 3/47 | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249316Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135240
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GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453646Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 723706
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 22, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 21
Find out detailed SpliceAI scores and Pangolin per-transcript scores at