rs756492434
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000719.7(CACNA1C):āc.5411T>Cā(p.Val1804Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,585,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000719.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.5411T>C | p.Val1804Ala | missense_variant | 42/47 | ENST00000399655.6 | NP_000710.5 | |
CACNA1C | NM_001167623.2 | c.5411T>C | p.Val1804Ala | missense_variant | 42/47 | ENST00000399603.6 | NP_001161095.1 | |
CACNA1C-AS1 | NR_045725.1 | n.334-1866A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.5411T>C | p.Val1804Ala | missense_variant | 42/47 | 5 | NM_001167623.2 | ENSP00000382512 | ||
CACNA1C | ENST00000399655.6 | c.5411T>C | p.Val1804Ala | missense_variant | 42/47 | 1 | NM_000719.7 | ENSP00000382563 | ||
CACNA1C-AS1 | ENST00000501371.5 | n.295-1866A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000982 AC: 2AN: 203592Hom.: 0 AF XY: 0.00000905 AC XY: 1AN XY: 110476
GnomAD4 exome AF: 0.0000105 AC: 15AN: 1433794Hom.: 0 Cov.: 34 AF XY: 0.0000127 AC XY: 9AN XY: 710254
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74318
ClinVar
Submissions by phenotype
Timothy syndrome;C2678478:Brugada syndrome 3;CN260585:Long qt syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 08, 2021 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 20, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 12, 2023 | 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