chr12-2685819-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_000719.7(CACNA1C):āc.5657G>Cā(p.Gly1886Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1886D) has been classified as Likely benign.
Frequency
Consequence
NM_000719.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.5657G>C | p.Gly1886Ala | missense_variant | 44/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.5657G>C | p.Gly1886Ala | missense_variant | 44/47 | ENST00000399603.6 | |
CACNA1C-AS1 | NR_045725.1 | n.333+4321C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.5657G>C | p.Gly1886Ala | missense_variant | 44/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.5657G>C | p.Gly1886Ala | missense_variant | 44/47 | 1 | NM_000719.7 | ||
CACNA1C-AS1 | ENST00000501371.5 | n.294+4321C>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248882Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135030
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1460970Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 726818
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces glycine with alanine at codon 1886 of the CACNA1C protein (p.Gly1886Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at