rs1325309
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000069.3(CACNA1S):c.153-61A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,421,418 control chromosomes in the GnomAD database, including 144,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.47 ( 17525 hom., cov: 33)
Exomes 𝑓: 0.44 ( 127380 hom. )
Consequence
CACNA1S
NM_000069.3 intron
NM_000069.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.916
Genes affected
CACNA1S (HGNC:1397): (calcium voltage-gated channel subunit alpha1 S) This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 1-201110330-T-A is Benign according to our data. Variant chr1-201110330-T-A is described in ClinVar as [Benign]. Clinvar id is 678214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201110330-T-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.153-61A>T | intron_variant | ENST00000362061.4 | |||
CACNA1S | XM_005245478.4 | c.153-61A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.153-61A>T | intron_variant | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.471 AC: 71609AN: 151986Hom.: 17499 Cov.: 33
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GnomAD4 exome AF: 0.442 AC: 561395AN: 1269314Hom.: 127380 AF XY: 0.444 AC XY: 284369AN XY: 640632
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GnomAD4 genome ? AF: 0.471 AC: 71686AN: 152104Hom.: 17525 Cov.: 33 AF XY: 0.473 AC XY: 35159AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypokalemic periodic paralysis, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at