rs374262237
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_021098.3(CACNA1H):c.3852C>A(p.Arg1284Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,552,080 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: 26)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
1
2
Clinical Significance
Conservation
PhyloP100: -3.19
Publications
1 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: Benign. The variant received -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 16-1210376-C-A is Benign according to our data. Variant chr16-1210376-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 585638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.19 with no splicing effect.
BS2
High AC in GnomAdExome4 at 56 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CACNA1H | NM_021098.3 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 35 | ENST00000348261.11 | NP_066921.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1H | ENST00000348261.11 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
| CACNA1H | ENST00000569107.6 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 34 | 1 | ENSP00000454990.2 | |||
| CACNA1H | ENST00000711493.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 34 | ENSP00000518778.1 | ||||
| CACNA1H | ENST00000565831.7 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 34 | 1 | ENSP00000455840.1 | |||
| CACNA1H | ENST00000711450.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 35 | ENSP00000518762.1 | ||||
| CACNA1H | ENST00000564231.6 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 35 | 1 | ENSP00000457555.2 | |||
| CACNA1H | ENST00000638323.1 | c.3813C>A | p.Arg1271Arg | synonymous_variant | Exon 19 of 35 | 5 | ENSP00000492267.1 | |||
| CACNA1H | ENST00000562079.6 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 34 | 1 | ENSP00000454581.2 | |||
| CACNA1H | ENST00000711438.1 | c.3813C>A | p.Arg1271Arg | synonymous_variant | Exon 19 of 34 | ENSP00000518754.1 | ||||
| CACNA1H | ENST00000711482.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 36 | ENSP00000518771.1 | ||||
| CACNA1H | ENST00000711485.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 35 | ENSP00000518774.1 | ||||
| CACNA1H | ENST00000711455.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 36 | ENSP00000518768.1 | ||||
| CACNA1H | ENST00000711483.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 35 | ENSP00000518772.1 | ||||
| CACNA1H | ENST00000711456.1 | c.3852C>A | p.Arg1284Arg | synonymous_variant | Exon 19 of 34 | ENSP00000518769.1 | ||||
| CACNA1H | ENST00000621827.2 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 37 | 6 | ENSP00000518766.1 | ||||
| CACNA1H | ENST00000637236.3 | n.3902C>A | non_coding_transcript_exon_variant | Exon 19 of 34 | 5 | ENSP00000492650.2 | ||||
| CACNA1H | ENST00000639478.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 35 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.*1765C>A | non_coding_transcript_exon_variant | Exon 19 of 35 | 5 | ENSP00000491488.1 | ||||
| CACNA1H | ENST00000711442.1 | n.*3299C>A | non_coding_transcript_exon_variant | Exon 18 of 34 | ENSP00000518758.1 | |||||
| CACNA1H | ENST00000711448.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 36 | ENSP00000518760.1 | |||||
| CACNA1H | ENST00000711449.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 35 | ENSP00000518761.1 | |||||
| CACNA1H | ENST00000711451.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 36 | ENSP00000518763.1 | |||||
| CACNA1H | ENST00000711452.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 36 | ENSP00000518764.1 | |||||
| CACNA1H | ENST00000711453.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 36 | ENSP00000518765.1 | |||||
| CACNA1H | ENST00000711484.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 35 | ENSP00000518773.1 | |||||
| CACNA1H | ENST00000711486.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 37 | ENSP00000518775.1 | |||||
| CACNA1H | ENST00000711487.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 36 | ENSP00000518776.1 | |||||
| CACNA1H | ENST00000711488.1 | n.3852C>A | non_coding_transcript_exon_variant | Exon 19 of 35 | ENSP00000518777.1 | |||||
| CACNA1H | ENST00000640028.1 | n.*1765C>A | 3_prime_UTR_variant | Exon 19 of 35 | 5 | ENSP00000491488.1 | ||||
| CACNA1H | ENST00000711442.1 | n.*3299C>A | 3_prime_UTR_variant | Exon 18 of 34 | ENSP00000518758.1 |
Frequencies
GnomAD3 genomes 0.00000664 AC: 1AN: 150700Hom.: 0 Cov.: 26 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
150700
Hom.:
Cov.:
26
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: 0.0000170 AC: 3AN: 176064 AF XY: 0.0000105 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
176064
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: 0.0000400 AC: 56AN: 1401380Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 28AN XY: 693526 show subpopulations
GnomAD4 exome
AF:
AC:
56
AN:
1401380
Hom.:
Cov.:
32
AF XY:
AC XY:
28
AN XY:
693526
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32308
American (AMR)
AF:
AC:
0
AN:
37890
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25288
East Asian (EAS)
AF:
AC:
0
AN:
37098
South Asian (SAS)
AF:
AC:
0
AN:
80378
European-Finnish (FIN)
AF:
AC:
0
AN:
40342
Middle Eastern (MID)
AF:
AC:
0
AN:
5710
European-Non Finnish (NFE)
AF:
AC:
56
AN:
1083864
Other (OTH)
AF:
AC:
0
AN:
58502
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<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 0.00000664 AC: 1AN: 150700Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 73460 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
150700
Hom.:
Cov.:
26
AF XY:
AC XY:
0
AN XY:
73460
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
40856
American (AMR)
AF:
AC:
0
AN:
15156
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3456
East Asian (EAS)
AF:
AC:
0
AN:
5074
South Asian (SAS)
AF:
AC:
0
AN:
4730
European-Finnish (FIN)
AF:
AC:
0
AN:
10506
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67642
Other (OTH)
AF:
AC:
0
AN:
2060
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
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.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Oct 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
Jul 05, 2018
Athena Diagnostics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
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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