rs59297244
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_021098.3(CACNA1H):c.6273C>T(p.Ala2091=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,556,898 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0057 ( 11 hom., cov: 35)
Exomes 𝑓: 0.00051 ( 2 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.99
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=-0.77).
BP6
?
Variant 16-1220205-C-T is Benign according to our data. Variant chr16-1220205-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.99 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00569 (866/152298) while in subpopulation AFR AF= 0.0194 (805/41564). AF 95% confidence interval is 0.0183. There are 11 homozygotes in gnomad4. There are 406 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 866 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.6273C>T | p.Ala2091= | synonymous_variant | 35/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.6273C>T | p.Ala2091= | synonymous_variant | 35/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00568 AC: 864AN: 152184Hom.: 11 Cov.: 35
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GnomAD3 exomes AF: 0.00127 AC: 238AN: 188062Hom.: 2 AF XY: 0.000984 AC XY: 104AN XY: 105648
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GnomAD4 exome AF: 0.000508 AC: 713AN: 1404600Hom.: 2 Cov.: 73 AF XY: 0.000453 AC XY: 315AN XY: 695956
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GnomAD4 genome ? AF: 0.00569 AC: 866AN: 152298Hom.: 11 Cov.: 35 AF XY: 0.00545 AC XY: 406AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 09, 2021 | - - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 25, 2017 | - - |
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