12-2115309-C-G
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000719.7(CACNA1C):c.135C>G(p.Thr45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000891 in 1,594,360 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T45T) has been classified as Likely benign.
Frequency
Consequence
NM_000719.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.135C>G | p.Thr45= | synonymous_variant | 2/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.135C>G | p.Thr45= | synonymous_variant | 2/47 | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.135C>G | p.Thr45= | synonymous_variant | 2/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.135C>G | p.Thr45= | synonymous_variant | 2/47 | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152242Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000285 AC: 6AN: 210722Hom.: 0 AF XY: 0.0000346 AC XY: 4AN XY: 115558
GnomAD4 exome AF: 0.0000915 AC: 132AN: 1442118Hom.: 0 Cov.: 32 AF XY: 0.0000949 AC XY: 68AN XY: 716192
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152242Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74384
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 10, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | CACNA1C: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 06, 2023 | - - |
CACNA1C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 08, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at