rs1555884916
Variant names:
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]
Genome browser will be placed here
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
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1C | ENST00000399603.6 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 5 | NM_001167623.2 | ENSP00000382512.1 | |||
| CACNA1C | ENST00000399655.6 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | NM_000719.7 | ENSP00000382563.1 | |||
| CACNA1C | ENST00000682544.1 | c.3708+9_3708+10insT | intron_variant | Intron 28 of 49 | ENSP00000507184.1 | |||||
| CACNA1C | ENST00000406454.8 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 47 | 5 | ENSP00000385896.3 | ||||
| CACNA1C | ENST00000399634.6 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 5 | ENSP00000382542.2 | ||||
| CACNA1C | ENST00000683824.1 | c.3723+9_3723+10insT | intron_variant | Intron 28 of 47 | ENSP00000507867.1 | |||||
| CACNA1C | ENST00000347598.9 | c.3618+9_3618+10insT | intron_variant | Intron 28 of 48 | 1 | ENSP00000266376.6 | ||||
| CACNA1C | ENST00000344100.7 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000341092.3 | ||||
| CACNA1C | ENST00000327702.12 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 47 | 1 | ENSP00000329877.7 | ||||
| CACNA1C | ENST00000399617.6 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 47 | 5 | ENSP00000382526.1 | ||||
| CACNA1C | ENST00000682462.1 | c.3648+9_3648+10insT | intron_variant | Intron 27 of 46 | ENSP00000507105.1 | |||||
| CACNA1C | ENST00000683781.1 | c.3648+9_3648+10insT | intron_variant | Intron 27 of 46 | ENSP00000507434.1 | |||||
| CACNA1C | ENST00000683840.1 | c.3648+9_3648+10insT | intron_variant | Intron 27 of 46 | ENSP00000507612.1 | |||||
| CACNA1C | ENST00000683956.1 | c.3648+9_3648+10insT | intron_variant | Intron 27 of 46 | ENSP00000506882.1 | |||||
| CACNA1C | ENST00000399638.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 47 | 1 | ENSP00000382547.1 | ||||
| CACNA1C | ENST00000335762.10 | c.3633+9_3633+10insT | intron_variant | Intron 28 of 47 | 5 | ENSP00000336982.5 | ||||
| CACNA1C | ENST00000399606.5 | c.3618+9_3618+10insT | intron_variant | Intron 28 of 47 | 1 | ENSP00000382515.1 | ||||
| CACNA1C | ENST00000399621.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382530.1 | ||||
| CACNA1C | ENST00000399637.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382546.1 | ||||
| CACNA1C | ENST00000402845.7 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000385724.3 | ||||
| CACNA1C | ENST00000399629.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382537.1 | ||||
| CACNA1C | ENST00000682336.1 | c.3633+9_3633+10insT | intron_variant | Intron 28 of 46 | ENSP00000507898.1 | |||||
| CACNA1C | ENST00000399591.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 45 | 1 | ENSP00000382500.1 | ||||
| CACNA1C | ENST00000399595.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 45 | 1 | ENSP00000382504.1 | ||||
| CACNA1C | ENST00000399649.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 45 | 1 | ENSP00000382557.1 | ||||
| CACNA1C | ENST00000399597.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382506.1 | ||||
| CACNA1C | ENST00000399601.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382510.1 | ||||
| CACNA1C | ENST00000399641.6 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382549.1 | ||||
| CACNA1C | ENST00000399644.5 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | 1 | ENSP00000382552.1 | ||||
| CACNA1C | ENST00000682835.1 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 46 | ENSP00000507282.1 | |||||
| CACNA1C | ENST00000683482.1 | c.3549+9_3549+10insT | intron_variant | Intron 27 of 46 | ENSP00000507169.1 | |||||
| CACNA1C | ENST00000682686.1 | c.3558+9_3558+10insT | intron_variant | Intron 27 of 45 | ENSP00000507309.1 | |||||
| CACNA1C | ENST00000480911.6 | n.*2165+9_*2165+10insT | intron_variant | Intron 25 of 26 | 5 | ENSP00000437936.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152140
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461316Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726908
GnomAD4 exome
AF:
AC:
3
AN:
1461316
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726908
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
GnomAD4 genome
AF:
AC:
1
AN:
152140
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74326
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Feb 05, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Long QT syndrome Benign:1
Dec 20, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at