rs41276706
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001129829.2(CACNA1C):c.4000G>A(p.Asp1334Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,613,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D1334D) has been classified as Benign.
Frequency
Consequence
NM_001129829.2 missense
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.3946-12G>A | intron_variant | ENST00000399655.6 | NP_000710.5 | |||
CACNA1C | NM_001167623.2 | c.3946-12G>A | intron_variant | ENST00000399603.6 | NP_001161095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000344100.7 | c.4000G>A | p.Asp1334Asn | missense_variant | 32/47 | 1 | ENSP00000341092.3 | |||
CACNA1C | ENST00000399603.6 | c.3946-12G>A | intron_variant | 5 | NM_001167623.2 | ENSP00000382512.1 | ||||
CACNA1C | ENST00000399655.6 | c.3946-12G>A | intron_variant | 1 | NM_000719.7 | ENSP00000382563.1 | ||||
CACNA1C | ENST00000682544.1 | c.4180-12G>A | intron_variant | ENSP00000507184.1 | ||||||
CACNA1C | ENST00000406454.8 | c.3946-12G>A | intron_variant | 5 | ENSP00000385896.3 | |||||
CACNA1C | ENST00000399634.6 | c.3913-12G>A | intron_variant | 5 | ENSP00000382542.2 | |||||
CACNA1C | ENST00000683824.1 | c.4111-12G>A | intron_variant | ENSP00000507867.1 | ||||||
CACNA1C | ENST00000347598.9 | c.4090-12G>A | intron_variant | 1 | ENSP00000266376.6 | |||||
CACNA1C | ENST00000327702.12 | c.3946-12G>A | intron_variant | 1 | ENSP00000329877.7 | |||||
CACNA1C | ENST00000399617.6 | c.3946-12G>A | intron_variant | 5 | ENSP00000382526.1 | |||||
CACNA1C | ENST00000682462.1 | c.4036-12G>A | intron_variant | ENSP00000507105.1 | ||||||
CACNA1C | ENST00000683781.1 | c.4036-12G>A | intron_variant | ENSP00000507434.1 | ||||||
CACNA1C | ENST00000683840.1 | c.4036-12G>A | intron_variant | ENSP00000507612.1 | ||||||
CACNA1C | ENST00000683956.1 | c.4036-12G>A | intron_variant | ENSP00000506882.1 | ||||||
CACNA1C | ENST00000399638.5 | c.4030-12G>A | intron_variant | 1 | ENSP00000382547.1 | |||||
CACNA1C | ENST00000335762.10 | c.4021-12G>A | intron_variant | 5 | ENSP00000336982.5 | |||||
CACNA1C | ENST00000399606.5 | c.4006-12G>A | intron_variant | 1 | ENSP00000382515.1 | |||||
CACNA1C | ENST00000399621.5 | c.3946-12G>A | intron_variant | 1 | ENSP00000382530.1 | |||||
CACNA1C | ENST00000399637.5 | c.3946-12G>A | intron_variant | 1 | ENSP00000382546.1 | |||||
CACNA1C | ENST00000402845.7 | c.3946-12G>A | intron_variant | 1 | ENSP00000385724.3 | |||||
CACNA1C | ENST00000399629.5 | c.3997-12G>A | intron_variant | 1 | ENSP00000382537.1 | |||||
CACNA1C | ENST00000682336.1 | c.3988-12G>A | intron_variant | ENSP00000507898.1 | ||||||
CACNA1C | ENST00000399591.5 | c.3913-12G>A | intron_variant | 1 | ENSP00000382500.1 | |||||
CACNA1C | ENST00000399595.5 | c.3913-12G>A | intron_variant | 1 | ENSP00000382504.1 | |||||
CACNA1C | ENST00000399649.5 | c.3907-12G>A | intron_variant | 1 | ENSP00000382557.1 | |||||
CACNA1C | ENST00000399597.5 | c.3946-12G>A | intron_variant | 1 | ENSP00000382506.1 | |||||
CACNA1C | ENST00000399601.5 | c.3946-12G>A | intron_variant | 1 | ENSP00000382510.1 | |||||
CACNA1C | ENST00000399641.6 | c.3946-12G>A | intron_variant | 1 | ENSP00000382549.1 | |||||
CACNA1C | ENST00000399644.5 | c.3946-12G>A | intron_variant | 1 | ENSP00000382552.1 | |||||
CACNA1C | ENST00000682835.1 | c.3946-12G>A | intron_variant | ENSP00000507282.1 | ||||||
CACNA1C | ENST00000683482.1 | c.3937-12G>A | intron_variant | ENSP00000507169.1 | ||||||
CACNA1C | ENST00000682686.1 | c.3913-12G>A | intron_variant | ENSP00000507309.1 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152098Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000233 AC: 58AN: 249296Hom.: 0 AF XY: 0.000311 AC XY: 42AN XY: 135238
GnomAD4 exome AF: 0.000315 AC: 461AN: 1461672Hom.: 2 Cov.: 33 AF XY: 0.000326 AC XY: 237AN XY: 727126
GnomAD4 genome AF: 0.000210 AC: 32AN: 152098Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74282
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:3
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2020 | This variant is associated with the following publications: (PMID: 26220970) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | CACNA1C: PP2, PP3 - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
CACNA1C-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 22, 2023 | 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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at