chr16-1202319-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_021098.3(CACNA1H):c.1869C>T(p.Ser623Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000777 in 1,582,448 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000062 ( 1 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 16-1202319-C-T is Benign according to our data. Variant chr16-1202319-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 529648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.54 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00023 (35/152334) while in subpopulation AFR AF= 0.000745 (31/41594). AF 95% confidence interval is 0.000539. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 35 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1H | ENST00000348261.11 | c.1869C>T | p.Ser623Ser | synonymous_variant | Exon 9 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
| CACNA1H | ENST00000565831.6 | c.1869C>T | p.Ser623Ser | synonymous_variant | Exon 8 of 33 | 1 | ENSP00000455840.1 | |||
| CACNA1H | ENST00000638323.1 | c.1830C>T | p.Ser610Ser | synonymous_variant | Exon 9 of 35 | 5 | ENSP00000492267.1 | |||
| CACNA1H | ENST00000639478.1 | n.1869C>T | non_coding_transcript_exon_variant | Exon 9 of 35 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.1385+484C>T | intron_variant | Intron 9 of 34 | 5 | ENSP00000491488.1 |
Frequencies
GnomAD3 genomes 0.000223 AC: 34AN: 152216Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000678 AC: 13AN: 191718Hom.: 1 AF XY: 0.0000570 AC XY: 6AN XY: 105186
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GnomAD4 exome AF: 0.0000615 AC: 88AN: 1430114Hom.: 1 Cov.: 56 AF XY: 0.0000677 AC XY: 48AN XY: 708618
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GnomAD4 genome 0.000230 AC: 35AN: 152334Hom.: 0 Cov.: 34 AF XY: 0.000228 AC XY: 17AN XY: 74490
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CACNA1H-related disorder Benign:1
Apr 10, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Sep 05, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at