12-2608721-C-CT
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_000719.7(CACNA1C):c.3558+10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CACNA1C
NM_000719.7 intron
NM_000719.7 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.390
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 Likely_benign. Variant got -6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 12-2608721-C-CT is Benign according to our data. Variant chr12-2608721-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 416851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CACNA1C | NM_000719.7 | c.3558+10dupT | intron_variant | ENST00000399655.6 | NP_000710.5 | |||
| CACNA1C | NM_001167623.2 | c.3558+10dupT | intron_variant | ENST00000399603.6 | NP_001161095.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1C | ENST00000399603.6 | c.3558+10dupT | intron_variant | 5 | NM_001167623.2 | ENSP00000382512.1 | ||||
| CACNA1C | ENST00000399655.6 | c.3558+10dupT | intron_variant | 1 | NM_000719.7 | ENSP00000382563.1 | ||||
| CACNA1C | ENST00000682544.1 | c.3708+10dupT | intron_variant | ENSP00000507184.1 | ||||||
| CACNA1C | ENST00000406454.8 | c.3558+10dupT | intron_variant | 5 | ENSP00000385896.3 | |||||
| CACNA1C | ENST00000399634.6 | c.3558+10dupT | intron_variant | 5 | ENSP00000382542.2 | |||||
| CACNA1C | ENST00000683824.1 | c.3723+10dupT | intron_variant | ENSP00000507867.1 | ||||||
| CACNA1C | ENST00000347598.9 | c.3618+10dupT | intron_variant | 1 | ENSP00000266376.6 | |||||
| CACNA1C | ENST00000344100.7 | c.3558+10dupT | intron_variant | 1 | ENSP00000341092.3 | |||||
| CACNA1C | ENST00000327702.12 | c.3558+10dupT | intron_variant | 1 | ENSP00000329877.7 | |||||
| CACNA1C | ENST00000399617.6 | c.3558+10dupT | intron_variant | 5 | ENSP00000382526.1 | |||||
| CACNA1C | ENST00000682462.1 | c.3648+10dupT | intron_variant | ENSP00000507105.1 | ||||||
| CACNA1C | ENST00000683781.1 | c.3648+10dupT | intron_variant | ENSP00000507434.1 | ||||||
| CACNA1C | ENST00000683840.1 | c.3648+10dupT | intron_variant | ENSP00000507612.1 | ||||||
| CACNA1C | ENST00000683956.1 | c.3648+10dupT | intron_variant | ENSP00000506882.1 | ||||||
| CACNA1C | ENST00000399638.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382547.1 | |||||
| CACNA1C | ENST00000335762.10 | c.3633+10dupT | intron_variant | 5 | ENSP00000336982.5 | |||||
| CACNA1C | ENST00000399606.5 | c.3618+10dupT | intron_variant | 1 | ENSP00000382515.1 | |||||
| CACNA1C | ENST00000399621.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382530.1 | |||||
| CACNA1C | ENST00000399637.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382546.1 | |||||
| CACNA1C | ENST00000402845.7 | c.3558+10dupT | intron_variant | 1 | ENSP00000385724.3 | |||||
| CACNA1C | ENST00000399629.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382537.1 | |||||
| CACNA1C | ENST00000682336.1 | c.3633+10dupT | intron_variant | ENSP00000507898.1 | ||||||
| CACNA1C | ENST00000399591.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382500.1 | |||||
| CACNA1C | ENST00000399595.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382504.1 | |||||
| CACNA1C | ENST00000399649.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382557.1 | |||||
| CACNA1C | ENST00000399597.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382506.1 | |||||
| CACNA1C | ENST00000399601.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382510.1 | |||||
| CACNA1C | ENST00000399641.6 | c.3558+10dupT | intron_variant | 1 | ENSP00000382549.1 | |||||
| CACNA1C | ENST00000399644.5 | c.3558+10dupT | intron_variant | 1 | ENSP00000382552.1 | |||||
| CACNA1C | ENST00000682835.1 | c.3558+10dupT | intron_variant | ENSP00000507282.1 | ||||||
| CACNA1C | ENST00000683482.1 | c.3549+10dupT | intron_variant | ENSP00000507169.1 | ||||||
| CACNA1C | ENST00000682686.1 | c.3558+10dupT | intron_variant | ENSP00000507309.1 | ||||||
| CACNA1C | ENST00000480911.6 | n.*2165+10dupT | intron_variant | 5 | ENSP00000437936.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461316Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726908
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GnomAD4 genome 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Long QT syndrome Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2020 | - - |
Computational scores
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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