rs115017320
Variant names:
Variant summary
Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000719.7(CACNA1C):c.3060G>A(p.Gln1020Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000434 in 1,613,534 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CACNA1C
NM_000719.7 synonymous
NM_000719.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 6.52
Publications
0 publications found
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 was made for transcript
Our verdict: Benign. The variant received -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 12-2605690-G-A is Benign according to our data. Variant chr12-2605690-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 416876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1C | ENST00000399603.6 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 5 | NM_001167623.2 | ENSP00000382512.1 | ||
| CACNA1C | ENST00000399655.6 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | NM_000719.7 | ENSP00000382563.1 | ||
| CACNA1C | ENST00000682544.1 | c.3210G>A | p.Gln1070Gln | synonymous_variant | Exon 25 of 50 | ENSP00000507184.1 | ||||
| CACNA1C | ENST00000406454.8 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 48 | 5 | ENSP00000385896.3 | |||
| CACNA1C | ENST00000399634.6 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 5 | ENSP00000382542.2 | |||
| CACNA1C | ENST00000683824.1 | c.3225G>A | p.Gln1075Gln | synonymous_variant | Exon 25 of 48 | ENSP00000507867.1 | ||||
| CACNA1C | ENST00000347598.9 | c.3120G>A | p.Gln1040Gln | synonymous_variant | Exon 25 of 49 | 1 | ENSP00000266376.6 | |||
| CACNA1C | ENST00000344100.7 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000341092.3 | |||
| CACNA1C | ENST00000327702.12 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 48 | 1 | ENSP00000329877.7 | |||
| CACNA1C | ENST00000399617.6 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 48 | 5 | ENSP00000382526.1 | |||
| CACNA1C | ENST00000682462.1 | c.3150G>A | p.Gln1050Gln | synonymous_variant | Exon 24 of 47 | ENSP00000507105.1 | ||||
| CACNA1C | ENST00000683781.1 | c.3150G>A | p.Gln1050Gln | synonymous_variant | Exon 24 of 47 | ENSP00000507434.1 | ||||
| CACNA1C | ENST00000683840.1 | c.3150G>A | p.Gln1050Gln | synonymous_variant | Exon 24 of 47 | ENSP00000507612.1 | ||||
| CACNA1C | ENST00000683956.1 | c.3150G>A | p.Gln1050Gln | synonymous_variant | Exon 24 of 47 | ENSP00000506882.1 | ||||
| CACNA1C | ENST00000399638.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 48 | 1 | ENSP00000382547.1 | |||
| CACNA1C | ENST00000335762.10 | c.3135G>A | p.Gln1045Gln | synonymous_variant | Exon 25 of 48 | 5 | ENSP00000336982.5 | |||
| CACNA1C | ENST00000399606.5 | c.3120G>A | p.Gln1040Gln | synonymous_variant | Exon 25 of 48 | 1 | ENSP00000382515.1 | |||
| CACNA1C | ENST00000399621.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382530.1 | |||
| CACNA1C | ENST00000399637.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382546.1 | |||
| CACNA1C | ENST00000402845.7 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000385724.3 | |||
| CACNA1C | ENST00000399629.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382537.1 | |||
| CACNA1C | ENST00000682336.1 | c.3135G>A | p.Gln1045Gln | synonymous_variant | Exon 25 of 47 | ENSP00000507898.1 | ||||
| CACNA1C | ENST00000399591.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 46 | 1 | ENSP00000382500.1 | |||
| CACNA1C | ENST00000399595.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 46 | 1 | ENSP00000382504.1 | |||
| CACNA1C | ENST00000399649.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 46 | 1 | ENSP00000382557.1 | |||
| CACNA1C | ENST00000399597.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382506.1 | |||
| CACNA1C | ENST00000399601.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382510.1 | |||
| CACNA1C | ENST00000399641.6 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382549.1 | |||
| CACNA1C | ENST00000399644.5 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | 1 | ENSP00000382552.1 | |||
| CACNA1C | ENST00000682835.1 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 47 | ENSP00000507282.1 | ||||
| CACNA1C | ENST00000683482.1 | c.3051G>A | p.Gln1017Gln | synonymous_variant | Exon 24 of 47 | ENSP00000507169.1 | ||||
| CACNA1C | ENST00000682686.1 | c.3060G>A | p.Gln1020Gln | synonymous_variant | Exon 24 of 46 | ENSP00000507309.1 | ||||
| CACNA1C | ENST00000480911.6 | n.*1667G>A | non_coding_transcript_exon_variant | Exon 22 of 27 | 5 | ENSP00000437936.2 | ||||
| CACNA1C | ENST00000480911.6 | n.*1667G>A | 3_prime_UTR_variant | Exon 22 of 27 | 5 | ENSP00000437936.2 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152184
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:
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251406 AF XY: 0.0000147 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
251406
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461232Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726942 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461232
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
726942
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33464
American (AMR)
AF:
AC:
0
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39688
South Asian (SAS)
AF:
AC:
0
AN:
86236
European-Finnish (FIN)
AF:
AC:
0
AN:
53388
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111484
Other (OTH)
AF:
AC:
1
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome 0.0000131 AC: 2AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74460 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152302
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74460
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41554
American (AMR)
AF:
AC:
0
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Long QT syndrome Benign:1
Oct 04, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Cardiovascular phenotype Benign:1
Jul 17, 2019
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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