rs565265907
Variant names:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_001128840.3(CACNA1D):c.1749C>T(p.Phe583Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,048 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
CACNA1D
NM_001128840.3 synonymous
NM_001128840.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.748
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 3-53723516-C-T is Benign according to our data. Variant chr3-53723516-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 505098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.748 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000723 (11/152188) while in subpopulation SAS AF= 0.000623 (3/4816). AF 95% confidence interval is 0.000169. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CACNA1D | NM_000720.4 | c.1809C>T | p.Phe603Phe | synonymous_variant | Exon 14 of 49 | ENST00000288139.11 | NP_000711.1 | |
| CACNA1D | NM_001128840.3 | c.1749C>T | p.Phe583Phe | synonymous_variant | Exon 13 of 48 | ENST00000350061.11 | NP_001122312.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1D | ENST00000288139.11 | c.1809C>T | p.Phe603Phe | synonymous_variant | Exon 14 of 49 | 1 | NM_000720.4 | ENSP00000288139.3 | ||
| CACNA1D | ENST00000350061.11 | c.1749C>T | p.Phe583Phe | synonymous_variant | Exon 13 of 48 | 1 | NM_001128840.3 | ENSP00000288133.5 |
Frequencies
GnomAD3 genomes 0.0000723 AC: 11AN: 152070Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251494Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135920
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GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 727238
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GnomAD4 genome 0.0000723 AC: 11AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74420
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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
Jun 05, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
p.Phe603Phe in exon 14 of CACNA1D: This variant is not expected to have clinical significance because it does not alter an amino acid residue and it is not loca ted within the splice consensus sequence. It has been identified in 7/121412 of the total chromosomes across several populations by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs565265907). -
not provided Benign:1
Jan 14, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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