rs1805032
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The ENST00000539935.7(CACNB4):c.1444C>T(p.Arg482*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CACNB4
ENST00000539935.7 stop_gained
ENST00000539935.7 stop_gained
Scores
5
1
Clinical Significance
Conservation
PhyloP100: 5.26
Publications
18 publications found
Genes affected
CACNB4 (HGNC:1404): (calcium voltage-gated channel auxiliary subunit beta 4) This gene encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein encoded by this locus plays an important role in calcium channel function by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE), juvenile myoclonic epilepsy (JME), and episodic ataxia, type 5. [provided by RefSeq, Aug 2016]
CACNB4 Gene-Disease associations (from GenCC):
- episodic ataxia type 5Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- juvenile myoclonic epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- epilepsy, idiopathic generalized, susceptibility to, 9Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- epilepsyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000539935.7. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNB4 | NM_000726.5 | MANE Select | c.1444C>T | p.Arg482* | stop_gained | Exon 14 of 14 | NP_000717.2 | ||
| CACNB4 | NM_001005746.4 | c.1390C>T | p.Arg464* | stop_gained | Exon 14 of 14 | NP_001005746.1 | |||
| CACNB4 | NM_001005747.4 | c.1342C>T | p.Arg448* | stop_gained | Exon 13 of 13 | NP_001005747.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNB4 | ENST00000539935.7 | TSL:1 MANE Select | c.1444C>T | p.Arg482* | stop_gained | Exon 14 of 14 | ENSP00000438949.1 | ||
| CACNB4 | ENST00000534999.7 | TSL:1 | c.1342C>T | p.Arg448* | stop_gained | Exon 13 of 13 | ENSP00000443893.1 | ||
| CACNB4 | ENST00000201943.10 | TSL:1 | c.1258C>T | p.Arg420* | stop_gained | Exon 13 of 13 | ENSP00000201943.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249086 AF XY: 0.00000740 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249086
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461290Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726970 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461290
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
726970
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53398
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111514
Other (OTH)
AF:
AC:
0
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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4
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<30
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions as Germline
Significance:risk factor
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
-
-
Epilepsy, juvenile myoclonic, susceptibility to, 6 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
PhyloP100
Vest4
GERP RS
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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