rs577701046
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_021098.3(CACNA1H):c.412-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
CACNA1H
NM_021098.3 splice_region, intron
NM_021098.3 splice_region, intron
Scores
2
Splicing: ADA: 0.9743
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.41
Publications
0 publications found
Genes affected
CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]
CACNA1H Gene-Disease associations (from GenCC):
- hyperaldosteronism, familial, type IVInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- childhood absence epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- epilepsy, childhood absence, susceptibility to, 6Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1H | ENST00000348261.11 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | 1 | NM_021098.3 | ENSP00000334198.7 | |||
| CACNA1H | ENST00000569107.6 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | 1 | ENSP00000454990.2 | ||||
| CACNA1H | ENST00000711493.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | ENSP00000518778.1 | |||||
| CACNA1H | ENST00000565831.7 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | 1 | ENSP00000455840.1 | ||||
| CACNA1H | ENST00000711450.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | ENSP00000518762.1 | |||||
| CACNA1H | ENST00000564231.6 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | 1 | ENSP00000457555.2 | ||||
| CACNA1H | ENST00000638323.1 | c.412-44C>A | intron_variant | Intron 3 of 34 | 5 | ENSP00000492267.1 | ||||
| CACNA1H | ENST00000562079.6 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | 1 | ENSP00000454581.2 | ||||
| CACNA1H | ENST00000711438.1 | c.412-44C>A | intron_variant | Intron 3 of 33 | ENSP00000518754.1 | |||||
| CACNA1H | ENST00000711482.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518771.1 | |||||
| CACNA1H | ENST00000711485.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | ENSP00000518774.1 | |||||
| CACNA1H | ENST00000711455.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518768.1 | |||||
| CACNA1H | ENST00000711483.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | ENSP00000518772.1 | |||||
| CACNA1H | ENST00000711456.1 | c.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | ENSP00000518769.1 | |||||
| CACNA1H | ENST00000621827.2 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 36 | 6 | ENSP00000518766.1 | ||||
| CACNA1H | ENST00000637236.3 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | 5 | ENSP00000492650.2 | ||||
| CACNA1H | ENST00000639478.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | 5 | ENSP00000491488.1 | ||||
| CACNA1H | ENST00000711442.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 33 | ENSP00000518758.1 | |||||
| CACNA1H | ENST00000711448.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518760.1 | |||||
| CACNA1H | ENST00000711449.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | ENSP00000518761.1 | |||||
| CACNA1H | ENST00000711451.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518763.1 | |||||
| CACNA1H | ENST00000711452.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518764.1 | |||||
| CACNA1H | ENST00000711453.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518765.1 | |||||
| CACNA1H | ENST00000711484.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | ENSP00000518773.1 | |||||
| CACNA1H | ENST00000711486.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 36 | ENSP00000518775.1 | |||||
| CACNA1H | ENST00000711487.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 35 | ENSP00000518776.1 | |||||
| CACNA1H | ENST00000711488.1 | n.412-5C>A | splice_region_variant, intron_variant | Intron 3 of 34 | ENSP00000518777.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1399468Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 690264 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1399468
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
690264
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31628
American (AMR)
AF:
AC:
0
AN:
35744
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25172
East Asian (EAS)
AF:
AC:
0
AN:
35760
South Asian (SAS)
AF:
AC:
0
AN:
79220
European-Finnish (FIN)
AF:
AC:
0
AN:
49328
Middle Eastern (MID)
AF:
AC:
0
AN:
5442
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1079162
Other (OTH)
AF:
AC:
0
AN:
58012
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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