rs3751662
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_021098.3(CACNA1H):c.300-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,604,724 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 Benign (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
CACNA1H
NM_021098.3 splice_region, splice_polypyrimidine_tract, intron
NM_021098.3 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001985
1
Clinical Significance
Conservation
PhyloP100: -1.15
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 -10 ACMG points.
BP6
?
Variant 16-1194964-G-A is Benign according to our data. Variant chr16-1194964-G-A is described in ClinVar as [Benign]. Clinvar id is 767495.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000204 (31/152238) while in subpopulation EAS AF= 0.00562 (29/5156). AF 95% confidence interval is 0.00402. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.300-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.300-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152120Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000473 AC: 117AN: 247178Hom.: 0 AF XY: 0.000423 AC XY: 57AN XY: 134660
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GnomAD4 exome AF: 0.000237 AC: 344AN: 1452486Hom.: 1 Cov.: 31 AF XY: 0.000217 AC XY: 157AN XY: 723032
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GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152238Hom.: 0 Cov.: 30 AF XY: 0.000255 AC XY: 19AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Benign
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