rs1263485007
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000720.4(CACNA1D):āc.649T>Cā(p.Leu217=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,910 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 (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
CACNA1D
NM_000720.4 synonymous
NM_000720.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.61
Genes affected
CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) 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, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 3-53660158-T-C is Benign according to our data. Variant chr3-53660158-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 517328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1D | NM_000720.4 | c.649T>C | p.Leu217= | synonymous_variant | 5/49 | ENST00000288139.11 | |
CACNA1D | NM_001128840.3 | c.649T>C | p.Leu217= | synonymous_variant | 5/48 | ENST00000350061.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1D | ENST00000288139.11 | c.649T>C | p.Leu217= | synonymous_variant | 5/49 | 1 | NM_000720.4 | P2 | |
CACNA1D | ENST00000350061.11 | c.649T>C | p.Leu217= | synonymous_variant | 5/48 | 1 | NM_001128840.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251246Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135786
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461698Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727174
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 13, 2017 | p.Leu217Leu in exon 5 of CACNA1D: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 01, 2022 | - - |
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