chr12-2688758-T-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000719.7(CACNA1C):c.6096T>C(p.Ser2032Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,563,238 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
CACNA1C
NM_000719.7 synonymous
NM_000719.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.734
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]
ITFG2-AS1 (HGNC:53128): (ITFG2 antisense RNA 1)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 12-2688758-T-C is Benign according to our data. Variant chr12-2688758-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 416878.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.734 with no splicing effect.
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CACNA1C | NM_000719.7 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | ENST00000399655.6 | NP_000710.5 | |
| CACNA1C | NM_001167623.2 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | ENST00000399603.6 | NP_001161095.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1C | ENST00000399603.6 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | 5 | NM_001167623.2 | ENSP00000382512.1 | ||
| CACNA1C | ENST00000399655.6 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | 1 | NM_000719.7 | ENSP00000382563.1 | ||
| CACNA1C | ENST00000682544.1 | c.6435T>C | p.Ser2145Ser | synonymous_variant | Exon 49 of 50 | ENSP00000507184.1 | ||||
| CACNA1C | ENST00000406454.8 | c.6309T>C | p.Ser2103Ser | synonymous_variant | Exon 47 of 48 | 5 | ENSP00000385896.3 | |||
| CACNA1C | ENST00000399634.6 | c.6276T>C | p.Ser2092Ser | synonymous_variant | Exon 46 of 47 | 5 | ENSP00000382542.2 | |||
| CACNA1C | ENST00000683824.1 | c.6261T>C | p.Ser2087Ser | synonymous_variant | Exon 47 of 48 | ENSP00000507867.1 | ||||
| CACNA1C | ENST00000347598.9 | c.6240T>C | p.Ser2080Ser | synonymous_variant | Exon 48 of 49 | 1 | ENSP00000266376.6 | |||
| CACNA1C | ENST00000344100.7 | c.6219T>C | p.Ser2073Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000341092.3 | |||
| CACNA1C | ENST00000327702.12 | c.6201T>C | p.Ser2067Ser | synonymous_variant | Exon 47 of 48 | 1 | ENSP00000329877.7 | |||
| CACNA1C | ENST00000399617.6 | c.6201T>C | p.Ser2067Ser | synonymous_variant | Exon 47 of 48 | 5 | ENSP00000382526.1 | |||
| CACNA1C | ENST00000682462.1 | c.6186T>C | p.Ser2062Ser | synonymous_variant | Exon 46 of 47 | ENSP00000507105.1 | ||||
| CACNA1C | ENST00000683781.1 | c.6186T>C | p.Ser2062Ser | synonymous_variant | Exon 46 of 47 | ENSP00000507434.1 | ||||
| CACNA1C | ENST00000683840.1 | c.6186T>C | p.Ser2062Ser | synonymous_variant | Exon 46 of 47 | ENSP00000507612.1 | ||||
| CACNA1C | ENST00000683956.1 | c.6186T>C | p.Ser2062Ser | synonymous_variant | Exon 46 of 47 | ENSP00000506882.1 | ||||
| CACNA1C | ENST00000399638.5 | c.6180T>C | p.Ser2060Ser | synonymous_variant | Exon 47 of 48 | 1 | ENSP00000382547.1 | |||
| CACNA1C | ENST00000335762.10 | c.6171T>C | p.Ser2057Ser | synonymous_variant | Exon 47 of 48 | 5 | ENSP00000336982.5 | |||
| CACNA1C | ENST00000399606.5 | c.6156T>C | p.Ser2052Ser | synonymous_variant | Exon 47 of 48 | 1 | ENSP00000382515.1 | |||
| CACNA1C | ENST00000399621.5 | c.6153T>C | p.Ser2051Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382530.1 | |||
| CACNA1C | ENST00000399637.5 | c.6153T>C | p.Ser2051Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382546.1 | |||
| CACNA1C | ENST00000402845.7 | c.6153T>C | p.Ser2051Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000385724.3 | |||
| CACNA1C | ENST00000399629.5 | c.6147T>C | p.Ser2049Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382537.1 | |||
| CACNA1C | ENST00000682336.1 | c.6138T>C | p.Ser2046Ser | synonymous_variant | Exon 46 of 47 | ENSP00000507898.1 | ||||
| CACNA1C | ENST00000399591.5 | c.6120T>C | p.Ser2040Ser | synonymous_variant | Exon 45 of 46 | 1 | ENSP00000382500.1 | |||
| CACNA1C | ENST00000399595.5 | c.6120T>C | p.Ser2040Ser | synonymous_variant | Exon 45 of 46 | 1 | ENSP00000382504.1 | |||
| CACNA1C | ENST00000399649.5 | c.6114T>C | p.Ser2038Ser | synonymous_variant | Exon 45 of 46 | 1 | ENSP00000382557.1 | |||
| CACNA1C | ENST00000399597.5 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382506.1 | |||
| CACNA1C | ENST00000399601.5 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382510.1 | |||
| CACNA1C | ENST00000399641.6 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382549.1 | |||
| CACNA1C | ENST00000399644.5 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | 1 | ENSP00000382552.1 | |||
| CACNA1C | ENST00000682835.1 | c.6096T>C | p.Ser2032Ser | synonymous_variant | Exon 46 of 47 | ENSP00000507282.1 | ||||
| CACNA1C | ENST00000683482.1 | c.6087T>C | p.Ser2029Ser | synonymous_variant | Exon 46 of 47 | ENSP00000507169.1 | ||||
| CACNA1C | ENST00000682686.1 | c.6063T>C | p.Ser2021Ser | synonymous_variant | Exon 45 of 46 | ENSP00000507309.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152060
Hom.:
Cov.:
33
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: 0.00 AC: 0AN: 184236 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
184236
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000156 AC: 22AN: 1411178Hom.: 0 Cov.: 32 AF XY: 0.0000158 AC XY: 11AN XY: 696920 show subpopulations
GnomAD4 exome
AF:
AC:
22
AN:
1411178
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
696920
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32316
American (AMR)
AF:
AC:
0
AN:
39146
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23910
East Asian (EAS)
AF:
AC:
0
AN:
38204
South Asian (SAS)
AF:
AC:
0
AN:
80150
European-Finnish (FIN)
AF:
AC:
0
AN:
46634
Middle Eastern (MID)
AF:
AC:
0
AN:
5588
European-Non Finnish (NFE)
AF:
AC:
21
AN:
1087002
Other (OTH)
AF:
AC:
1
AN:
58228
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
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<30
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35-40
40-45
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60-65
65-70
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>80
Age
GnomAD4 genome 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74270 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152060
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74270
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5178
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67980
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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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
Alfa
AF:
Hom.:
Bravo
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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
Dec 14, 2022
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
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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