chr12-2607008-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_000719.7(CACNA1C):c.3234C>T(p.Asp1078Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00096 in 1,613,952 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000719.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | ENST00000399655.6 | NP_000710.5 | |
CACNA1C | NM_001167623.2 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | ENST00000399603.6 | NP_001161095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 5 | NM_001167623.2 | ENSP00000382512.1 | ||
CACNA1C | ENST00000399655.6 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | NM_000719.7 | ENSP00000382563.1 | ||
CACNA1C | ENST00000682544.1 | c.3384C>T | p.Asp1128Asp | synonymous_variant | Exon 27 of 50 | ENSP00000507184.1 | ||||
CACNA1C | ENST00000406454.8 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 48 | 5 | ENSP00000385896.3 | |||
CACNA1C | ENST00000399634.6 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 5 | ENSP00000382542.2 | |||
CACNA1C | ENST00000683824.1 | c.3399C>T | p.Asp1133Asp | synonymous_variant | Exon 27 of 48 | ENSP00000507867.1 | ||||
CACNA1C | ENST00000347598.9 | c.3294C>T | p.Asp1098Asp | synonymous_variant | Exon 27 of 49 | 1 | ENSP00000266376.6 | |||
CACNA1C | ENST00000344100.7 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000341092.3 | |||
CACNA1C | ENST00000327702.12 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 48 | 1 | ENSP00000329877.7 | |||
CACNA1C | ENST00000399617.6 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 48 | 5 | ENSP00000382526.1 | |||
CACNA1C | ENST00000682462.1 | c.3324C>T | p.Asp1108Asp | synonymous_variant | Exon 26 of 47 | ENSP00000507105.1 | ||||
CACNA1C | ENST00000683781.1 | c.3324C>T | p.Asp1108Asp | synonymous_variant | Exon 26 of 47 | ENSP00000507434.1 | ||||
CACNA1C | ENST00000683840.1 | c.3324C>T | p.Asp1108Asp | synonymous_variant | Exon 26 of 47 | ENSP00000507612.1 | ||||
CACNA1C | ENST00000683956.1 | c.3324C>T | p.Asp1108Asp | synonymous_variant | Exon 26 of 47 | ENSP00000506882.1 | ||||
CACNA1C | ENST00000399638.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 48 | 1 | ENSP00000382547.1 | |||
CACNA1C | ENST00000335762.10 | c.3309C>T | p.Asp1103Asp | synonymous_variant | Exon 27 of 48 | 5 | ENSP00000336982.5 | |||
CACNA1C | ENST00000399606.5 | c.3294C>T | p.Asp1098Asp | synonymous_variant | Exon 27 of 48 | 1 | ENSP00000382515.1 | |||
CACNA1C | ENST00000399621.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382530.1 | |||
CACNA1C | ENST00000399637.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382546.1 | |||
CACNA1C | ENST00000402845.7 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000385724.3 | |||
CACNA1C | ENST00000399629.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382537.1 | |||
CACNA1C | ENST00000682336.1 | c.3309C>T | p.Asp1103Asp | synonymous_variant | Exon 27 of 47 | ENSP00000507898.1 | ||||
CACNA1C | ENST00000399591.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 46 | 1 | ENSP00000382500.1 | |||
CACNA1C | ENST00000399595.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 46 | 1 | ENSP00000382504.1 | |||
CACNA1C | ENST00000399649.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 46 | 1 | ENSP00000382557.1 | |||
CACNA1C | ENST00000399597.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382506.1 | |||
CACNA1C | ENST00000399601.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382510.1 | |||
CACNA1C | ENST00000399641.6 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382549.1 | |||
CACNA1C | ENST00000399644.5 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | 1 | ENSP00000382552.1 | |||
CACNA1C | ENST00000682835.1 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 47 | ENSP00000507282.1 | ||||
CACNA1C | ENST00000683482.1 | c.3225C>T | p.Asp1075Asp | synonymous_variant | Exon 26 of 47 | ENSP00000507169.1 | ||||
CACNA1C | ENST00000682686.1 | c.3234C>T | p.Asp1078Asp | synonymous_variant | Exon 26 of 46 | ENSP00000507309.1 | ||||
CACNA1C | ENST00000480911.6 | n.*1841C>T | non_coding_transcript_exon_variant | Exon 24 of 27 | 5 | ENSP00000437936.2 | ||||
CACNA1C | ENST00000480911.6 | n.*1841C>T | 3_prime_UTR_variant | Exon 24 of 27 | 5 | ENSP00000437936.2 |
Frequencies
GnomAD3 genomes AF: 0.000795 AC: 121AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000867 AC: 216AN: 249226Hom.: 2 AF XY: 0.000865 AC XY: 117AN XY: 135214
GnomAD4 exome AF: 0.000978 AC: 1429AN: 1461664Hom.: 4 Cov.: 31 AF XY: 0.00102 AC XY: 745AN XY: 727120
GnomAD4 genome AF: 0.000795 AC: 121AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.000765 AC XY: 57AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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CACNA1C: BP4, BP7, BS1 -
not specified Benign:3
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Timothy syndrome;C2678478:Brugada syndrome 3;C5774213:Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures;CN260585:Long qt syndrome 8 Benign:1
This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.4% [41/10356] including 2 total homozygotes; https://gnomad.broadinstitute.org/variant/12-2716174-C-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:195932). Of note, this variant is a silent variant and does not change the amino acid, is not predicted to impact splicing, and this nucleotide position is poorly conserved evolutionarily, reducing the probability that this variant is disease-causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -
Long QT syndrome Benign:1
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Cardiovascular phenotype Benign:1
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