rs540579196
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001127222.2(CACNA1A):c.1212C>T(p.Leu404Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
CACNA1A
NM_001127222.2 synonymous
NM_001127222.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.174
Genes affected
CACNA1A (HGNC:1388): (calcium voltage-gated channel subunit alpha1 A) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 19-13332912-G-A is Benign according to our data. Variant chr19-13332912-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 751967.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.174 with no splicing effect.
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
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CACNA1A | ENST00000360228.11 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 1 | NM_001127222.2 | ENSP00000353362.5 | ||
CACNA1A | ENST00000638029.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/48 | 5 | ENSP00000489829.1 | |||
CACNA1A | ENST00000573710.7 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 5 | ENSP00000460092.3 | |||
CACNA1A | ENST00000635727.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 5 | ENSP00000490001.1 | |||
CACNA1A | ENST00000637769.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 1 | ENSP00000489778.1 | |||
CACNA1A | ENST00000636012.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/46 | 5 | ENSP00000490223.1 | |||
CACNA1A | ENST00000637736.1 | c.1071C>T | p.Leu357Leu | synonymous_variant | 8/46 | 5 | ENSP00000489861.1 | |||
CACNA1A | ENST00000636389.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 5 | ENSP00000489992.1 | |||
CACNA1A | ENST00000637432.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/48 | 5 | ENSP00000490617.1 | |||
CACNA1A | ENST00000636549.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/48 | 5 | ENSP00000490578.1 | |||
CACNA1A | ENST00000637927.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 5 | ENSP00000489715.1 | |||
CACNA1A | ENST00000635895.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 5 | ENSP00000490323.1 | |||
CACNA1A | ENST00000638009.2 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/47 | 1 | ENSP00000489913.1 | |||
CACNA1A | ENST00000637276.1 | c.1212C>T | p.Leu404Leu | synonymous_variant | 9/46 | 5 | ENSP00000489777.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152098Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000323 AC: 8AN: 248002Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134538
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460086Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6AN XY: 726384
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152098Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74288
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 23, 2020 | - - |
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