NM_001205293.3:c.36A>G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001205293.3(CACNA1E):c.36A>G(p.Pro12Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,394 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: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CACNA1E
NM_001205293.3 synonymous
NM_001205293.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.126
Genes affected
CACNA1E (HGNC:1392): (calcium voltage-gated channel subunit alpha1 E) Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 1-181483780-A-G is Benign according to our data. Variant chr1-181483780-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1536733.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.126 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1E | ENST00000367573.7 | c.36A>G | p.Pro12Pro | synonymous_variant | Exon 1 of 48 | 1 | NM_001205293.3 | ENSP00000356545.2 | ||
| CACNA1E | ENST00000360108.7 | c.36A>G | p.Pro12Pro | synonymous_variant | Exon 1 of 47 | 5 | ENSP00000353222.3 | |||
| CACNA1E | ENST00000367570.6 | c.36A>G | p.Pro12Pro | synonymous_variant | Exon 1 of 47 | 1 | ENSP00000356542.1 | |||
| CACNA1E | ENST00000621791.4 | c.36A>G | p.Pro12Pro | synonymous_variant | Exon 1 of 46 | 1 | ENSP00000481619.1 | |||
| CACNA1E | ENST00000524607.6 | c.471A>G | p.Pro157Pro | synonymous_variant | Exon 3 of 12 | 5 | ENSP00000432038.2 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151732Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151732
Hom.:
Cov.:
31
Gnomad AFR
AF:
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000121 AC: 3AN: 248006 AF XY: 0.0000149 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
248006
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458662Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725628 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1458662
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
725628
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33416
American (AMR)
AF:
AC:
3
AN:
44684
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26082
East Asian (EAS)
AF:
AC:
0
AN:
39666
South Asian (SAS)
AF:
AC:
0
AN:
86134
European-Finnish (FIN)
AF:
AC:
0
AN:
53304
Middle Eastern (MID)
AF:
AC:
0
AN:
5048
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1110112
Other (OTH)
AF:
AC:
0
AN:
60216
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000659 AC: 1AN: 151732Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74078 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151732
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74078
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41312
American (AMR)
AF:
AC:
1
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5096
South Asian (SAS)
AF:
AC:
0
AN:
4798
European-Finnish (FIN)
AF:
AC:
0
AN:
10564
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67944
Other (OTH)
AF:
AC:
0
AN:
2076
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
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Aug 13, 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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