rs60415676
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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):āc.1479T>Cā(p.Ser493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,549,862 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0040 ( 4 hom., cov: 34)
Exomes š: 0.00043 ( 2 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.430
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=-0.93).
BP6
?
Variant 16-1201929-T-C is Benign according to our data. Variant chr16-1201929-T-C is described in ClinVar as [Benign]. Clinvar id is 460046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.43 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00395 (602/152326) while in subpopulation AFR AF= 0.014 (583/41582). AF 95% confidence interval is 0.0131. There are 4 homozygotes in gnomad4. There are 266 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 602 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.1479T>C | p.Ser493= | synonymous_variant | 9/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.1479T>C | p.Ser493= | synonymous_variant | 9/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00395 AC: 601AN: 152208Hom.: 4 Cov.: 34
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GnomAD3 exomes AF: 0.000817 AC: 121AN: 148134Hom.: 0 AF XY: 0.000541 AC XY: 43AN XY: 79446
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GnomAD4 exome AF: 0.000433 AC: 605AN: 1397536Hom.: 2 Cov.: 36 AF XY: 0.000383 AC XY: 264AN XY: 689274
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GnomAD4 genome ? AF: 0.00395 AC: 602AN: 152326Hom.: 4 Cov.: 34 AF XY: 0.00357 AC XY: 266AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:2
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
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 06, 2021 | - - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Computational scores
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Name
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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