3-53735452-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000720.4(CACNA1D):c.2760C>T(p.Ser920=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,234 control chromosomes in the GnomAD database, including 84,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.26 ( 6327 hom., cov: 33)
Exomes 𝑓: 0.32 ( 78323 hom. )
Consequence
CACNA1D
NM_000720.4 synonymous
NM_000720.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.01
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 3-53735452-C-T is Benign according to our data. Variant chr3-53735452-C-T is described in ClinVar as [Benign]. Clinvar id is 226470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-53735452-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.01 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1D | NM_000720.4 | c.2760C>T | p.Ser920= | synonymous_variant | 21/49 | ENST00000288139.11 | |
CACNA1D | NM_001128840.3 | c.2700C>T | p.Ser900= | synonymous_variant | 20/48 | ENST00000350061.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1D | ENST00000288139.11 | c.2760C>T | p.Ser920= | synonymous_variant | 21/49 | 1 | NM_000720.4 | P2 | |
CACNA1D | ENST00000350061.11 | c.2700C>T | p.Ser900= | synonymous_variant | 20/48 | 1 | NM_001128840.3 |
Frequencies
GnomAD3 genomes AF: 0.259 AC: 39384AN: 152078Hom.: 6324 Cov.: 33
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GnomAD3 exomes AF: 0.302 AC: 75995AN: 251442Hom.: 12488 AF XY: 0.303 AC XY: 41177AN XY: 135906
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GnomAD4 exome AF: 0.322 AC: 471051AN: 1461038Hom.: 78323 Cov.: 36 AF XY: 0.321 AC XY: 233045AN XY: 726902
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GnomAD4 genome AF: 0.259 AC: 39398AN: 152196Hom.: 6327 Cov.: 33 AF XY: 0.259 AC XY: 19286AN XY: 74394
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Ser920Ser in exon 21 of CACNA1D: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 34.9% (3003/8600) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1045958). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | 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. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Aldosterone-producing adenoma with seizures and neurological abnormalities Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Sinoatrial node dysfunction and deafness Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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