16-1204038-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_021098.3(CACNA1H):c.2031G>T(p.Ser677Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S677S) has been classified as Benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -4.73
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: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP7
Synonymous conserved (PhyloP=-4.73 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1H | ENST00000348261.11 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
| CACNA1H | ENST00000569107.6 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 34 | 1 | ENSP00000454990.2 | |||
| CACNA1H | ENST00000711493.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 34 | ENSP00000518778.1 | ||||
| CACNA1H | ENST00000565831.7 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 34 | 1 | ENSP00000455840.1 | |||
| CACNA1H | ENST00000711450.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 35 | ENSP00000518762.1 | ||||
| CACNA1H | ENST00000564231.6 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 35 | 1 | ENSP00000457555.2 | |||
| CACNA1H | ENST00000638323.1 | c.1992G>T | p.Ser664Ser | synonymous_variant | Exon 10 of 35 | 5 | ENSP00000492267.1 | |||
| CACNA1H | ENST00000562079.6 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 34 | 1 | ENSP00000454581.2 | |||
| CACNA1H | ENST00000711438.1 | c.1992G>T | p.Ser664Ser | synonymous_variant | Exon 10 of 34 | ENSP00000518754.1 | ||||
| CACNA1H | ENST00000711482.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 36 | ENSP00000518771.1 | ||||
| CACNA1H | ENST00000711485.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 35 | ENSP00000518774.1 | ||||
| CACNA1H | ENST00000711455.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 36 | ENSP00000518768.1 | ||||
| CACNA1H | ENST00000711483.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 35 | ENSP00000518772.1 | ||||
| CACNA1H | ENST00000711456.1 | c.2031G>T | p.Ser677Ser | synonymous_variant | Exon 10 of 34 | ENSP00000518769.1 | ||||
| CACNA1H | ENST00000621827.2 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 37 | 6 | ENSP00000518766.1 | ||||
| CACNA1H | ENST00000637236.3 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 34 | 5 | ENSP00000492650.2 | ||||
| CACNA1H | ENST00000639478.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 35 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.1414G>T | non_coding_transcript_exon_variant | Exon 10 of 35 | 5 | ENSP00000491488.1 | ||||
| CACNA1H | ENST00000711442.1 | n.*1478G>T | non_coding_transcript_exon_variant | Exon 9 of 34 | ENSP00000518758.1 | |||||
| CACNA1H | ENST00000711448.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 36 | ENSP00000518760.1 | |||||
| CACNA1H | ENST00000711449.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 35 | ENSP00000518761.1 | |||||
| CACNA1H | ENST00000711451.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 36 | ENSP00000518763.1 | |||||
| CACNA1H | ENST00000711452.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 36 | ENSP00000518764.1 | |||||
| CACNA1H | ENST00000711453.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 36 | ENSP00000518765.1 | |||||
| CACNA1H | ENST00000711484.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 35 | ENSP00000518773.1 | |||||
| CACNA1H | ENST00000711486.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 37 | ENSP00000518775.1 | |||||
| CACNA1H | ENST00000711487.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 36 | ENSP00000518776.1 | |||||
| CACNA1H | ENST00000711488.1 | n.2031G>T | non_coding_transcript_exon_variant | Exon 10 of 35 | ENSP00000518777.1 | |||||
| CACNA1H | ENST00000711442.1 | n.*1478G>T | 3_prime_UTR_variant | Exon 9 of 34 | ENSP00000518758.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1420220Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1AN XY: 702832 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1420220
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
702832
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32472
American (AMR)
AF:
AC:
0
AN:
39838
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25408
East Asian (EAS)
AF:
AC:
0
AN:
37336
South Asian (SAS)
AF:
AC:
0
AN:
81434
European-Finnish (FIN)
AF:
AC:
1
AN:
47312
Middle Eastern (MID)
AF:
AC:
0
AN:
5704
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1091878
Other (OTH)
AF:
AC:
0
AN:
58838
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
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
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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