rs769297492
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000719.7(CACNA1C):c.5138A>G(p.Asp1713Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000181 in 1,605,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1713E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000719.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.5138A>G | p.Asp1713Gly | missense_variant | 42/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.5138A>G | p.Asp1713Gly | missense_variant | 42/47 | ENST00000399603.6 | |
CACNA1C-AS1 | NR_045725.1 | n.334-1593T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.5138A>G | p.Asp1713Gly | missense_variant | 42/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.5138A>G | p.Asp1713Gly | missense_variant | 42/47 | 1 | NM_000719.7 | ||
CACNA1C-AS1 | ENST00000501371.5 | n.295-1593T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152024Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000292 AC: 7AN: 239324Hom.: 0 AF XY: 0.0000231 AC XY: 3AN XY: 130138
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1453046Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8AN XY: 721676
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74396
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 02, 2022 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 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