rs1544515
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000719.7(CACNA1C):c.617+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,503,642 control chromosomes in the GnomAD database, including 48,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.27 ( 5594 hom., cov: 32)
Exomes 𝑓: 0.25 ( 43383 hom. )
Consequence
CACNA1C
NM_000719.7 intron
NM_000719.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.741
Genes affected
CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]
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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=-0.91).
BP6
?
Variant 12-2449132-G-A is Benign according to our data. Variant chr12-2449132-G-A is described in ClinVar as [Benign]. Clinvar id is 93420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-2449132-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.617+17G>A | intron_variant | ENST00000399655.6 | |||
CACNA1C | NM_001167623.2 | c.617+17G>A | intron_variant | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.617+17G>A | intron_variant | 5 | NM_001167623.2 | ||||
CACNA1C | ENST00000399655.6 | c.617+17G>A | intron_variant | 1 | NM_000719.7 | ||||
ENST00000649808.1 | n.208+21C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.269 AC: 40815AN: 151714Hom.: 5583 Cov.: 32
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GnomAD3 exomes AF: 0.251 AC: 34268AN: 136684Hom.: 4403 AF XY: 0.254 AC XY: 18151AN XY: 71382
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GnomAD4 exome AF: 0.250 AC: 338422AN: 1351810Hom.: 43383 Cov.: 28 AF XY: 0.252 AC XY: 167424AN XY: 663532
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GnomAD4 genome ? AF: 0.269 AC: 40875AN: 151832Hom.: 5594 Cov.: 32 AF XY: 0.269 AC XY: 19936AN XY: 74190
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 23, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2011 | 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. - |
Timothy syndrome 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 | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Long QT syndrome 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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at