rs1555884613
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000719.7(CACNA1C):c.3420G>A(p.Val1140Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000684 in 1,461,560 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: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CACNA1C
NM_000719.7 synonymous
NM_000719.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.78
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]
CACNA1C Gene-Disease associations (from GenCC):
- Timothy syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizuresInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- long QT syndromeInheritance: AD Classification: MODERATE Submitted by: ClinGen
- long QT syndrome 8Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- Brugada syndromeInheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, ClinGen
- Brugada syndrome 3Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- intellectual disabilityInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- short QT syndromeInheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 12-2608574-G-A is Benign according to our data. Variant chr12-2608574-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 526912.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | ENST00000399655.6 | NP_000710.5 | |
CACNA1C | NM_001167623.2 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | ENST00000399603.6 | NP_001161095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 5 | NM_001167623.2 | ENSP00000382512.1 | ||
CACNA1C | ENST00000399655.6 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | NM_000719.7 | ENSP00000382563.1 | ||
CACNA1C | ENST00000682544.1 | c.3570G>A | p.Val1190Val | synonymous_variant | Exon 28 of 50 | ENSP00000507184.1 | ||||
CACNA1C | ENST00000406454.8 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 48 | 5 | ENSP00000385896.3 | |||
CACNA1C | ENST00000399634.6 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 5 | ENSP00000382542.2 | |||
CACNA1C | ENST00000683824.1 | c.3585G>A | p.Val1195Val | synonymous_variant | Exon 28 of 48 | ENSP00000507867.1 | ||||
CACNA1C | ENST00000347598.9 | c.3480G>A | p.Val1160Val | synonymous_variant | Exon 28 of 49 | 1 | ENSP00000266376.6 | |||
CACNA1C | ENST00000344100.7 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000341092.3 | |||
CACNA1C | ENST00000327702.12 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 48 | 1 | ENSP00000329877.7 | |||
CACNA1C | ENST00000399617.6 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 48 | 5 | ENSP00000382526.1 | |||
CACNA1C | ENST00000682462.1 | c.3510G>A | p.Val1170Val | synonymous_variant | Exon 27 of 47 | ENSP00000507105.1 | ||||
CACNA1C | ENST00000683781.1 | c.3510G>A | p.Val1170Val | synonymous_variant | Exon 27 of 47 | ENSP00000507434.1 | ||||
CACNA1C | ENST00000683840.1 | c.3510G>A | p.Val1170Val | synonymous_variant | Exon 27 of 47 | ENSP00000507612.1 | ||||
CACNA1C | ENST00000683956.1 | c.3510G>A | p.Val1170Val | synonymous_variant | Exon 27 of 47 | ENSP00000506882.1 | ||||
CACNA1C | ENST00000399638.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 48 | 1 | ENSP00000382547.1 | |||
CACNA1C | ENST00000335762.10 | c.3495G>A | p.Val1165Val | synonymous_variant | Exon 28 of 48 | 5 | ENSP00000336982.5 | |||
CACNA1C | ENST00000399606.5 | c.3480G>A | p.Val1160Val | synonymous_variant | Exon 28 of 48 | 1 | ENSP00000382515.1 | |||
CACNA1C | ENST00000399621.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382530.1 | |||
CACNA1C | ENST00000399637.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382546.1 | |||
CACNA1C | ENST00000402845.7 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000385724.3 | |||
CACNA1C | ENST00000399629.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382537.1 | |||
CACNA1C | ENST00000682336.1 | c.3495G>A | p.Val1165Val | synonymous_variant | Exon 28 of 47 | ENSP00000507898.1 | ||||
CACNA1C | ENST00000399591.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 46 | 1 | ENSP00000382500.1 | |||
CACNA1C | ENST00000399595.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 46 | 1 | ENSP00000382504.1 | |||
CACNA1C | ENST00000399649.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 46 | 1 | ENSP00000382557.1 | |||
CACNA1C | ENST00000399597.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382506.1 | |||
CACNA1C | ENST00000399601.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382510.1 | |||
CACNA1C | ENST00000399641.6 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382549.1 | |||
CACNA1C | ENST00000399644.5 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | 1 | ENSP00000382552.1 | |||
CACNA1C | ENST00000682835.1 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 47 | ENSP00000507282.1 | ||||
CACNA1C | ENST00000683482.1 | c.3411G>A | p.Val1137Val | synonymous_variant | Exon 27 of 47 | ENSP00000507169.1 | ||||
CACNA1C | ENST00000682686.1 | c.3420G>A | p.Val1140Val | synonymous_variant | Exon 27 of 46 | ENSP00000507309.1 | ||||
CACNA1C | ENST00000480911.6 | n.*2027G>A | non_coding_transcript_exon_variant | Exon 25 of 27 | 5 | ENSP00000437936.2 | ||||
CACNA1C | ENST00000480911.6 | n.*2027G>A | 3_prime_UTR_variant | Exon 25 of 27 | 5 | ENSP00000437936.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461560Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727076 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461560
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727076
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86206
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111812
Other (OTH)
AF:
AC:
0
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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
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
75-80
>80
Age
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Long QT syndrome Benign:1
Feb 24, 2024
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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