NM_201596.3:c.912G>A
Variant names:
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS2
The NM_201596.3(CACNB2):c.912G>A(p.Leu304Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,674 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CACNB2
NM_201596.3 synonymous
NM_201596.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.175
Publications
0 publications found
Genes affected
CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]
CACNB2 Gene-Disease associations (from GenCC):
- Brugada syndrome 4Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine
- Brugada syndrome 1Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- short QT syndromeInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 10-18518936-G-A is Benign according to our data. Variant chr10-18518936-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 537375.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.175 with no splicing effect.
BS2
High AC in GnomAdExome4 at 5 AD,Unknown gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.912G>A | p.Leu304Leu | synonymous_variant | Exon 9 of 14 | 1 | NM_201596.3 | ENSP00000320025.8 | ||
CACNB2 | ENST00000377329.10 | c.750G>A | p.Leu250Leu | synonymous_variant | Exon 8 of 13 | 1 | NM_201590.3 | ENSP00000366546.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461674Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727158 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461674
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
727158
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39688
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111854
Other (OTH)
AF:
AC:
1
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.555
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
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>80
Age
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome 4 Benign:1
May 28, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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