9-137882854-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_000718.4(CACNA1B):c.501C>T(p.Asn167Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CACNA1B
NM_000718.4 synonymous
NM_000718.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.13
Publications
36 publications found
Genes affected
CACNA1B (HGNC:1389): (calcium voltage-gated channel subunit alpha1 B) The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
CACNA1B Gene-Disease associations (from GenCC):
- neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movementsInheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- complex neurodevelopmental disorder with motor featuresInheritance: AR Classification: MODERATE Submitted by: ClinGen
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
Synonymous conserved (PhyloP=-1.13 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CACNA1B | NM_000718.4 | c.501C>T | p.Asn167Asn | synonymous_variant | Exon 3 of 47 | ENST00000371372.6 | NP_000709.1 | |
| CACNA1B | NM_001243812.2 | c.501C>T | p.Asn167Asn | synonymous_variant | Exon 3 of 47 | NP_001230741.1 | ||
| CACNA1B-AS2 | NR_121583.1 | n.2674G>A | non_coding_transcript_exon_variant | Exon 2 of 4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1B | ENST00000371372.6 | c.501C>T | p.Asn167Asn | synonymous_variant | Exon 3 of 47 | 5 | NM_000718.4 | ENSP00000360423.1 | ||
| CACNA1B | ENST00000371357.5 | c.501C>T | p.Asn167Asn | synonymous_variant | Exon 3 of 46 | 5 | ENSP00000360408.1 | |||
| CACNA1B | ENST00000371363.5 | c.501C>T | p.Asn167Asn | synonymous_variant | Exon 3 of 46 | 5 | ENSP00000360414.1 | |||
| CACNA1B | ENST00000277551.6 | c.501C>T | p.Asn167Asn | synonymous_variant | Exon 3 of 47 | 5 | ENSP00000277551.2 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152198
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 249262 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
249262
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: 0.0000109 AC: 16AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727104 show subpopulations
GnomAD4 exome
AF:
AC:
16
AN:
1461636
Hom.:
Cov.:
31
AF XY:
AC XY:
9
AN XY:
727104
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33478
American (AMR)
AF:
AC:
1
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
5
AN:
39700
South Asian (SAS)
AF:
AC:
2
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53390
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1111826
Other (OTH)
AF:
AC:
1
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.459
Heterozygous variant carriers
0
1
2
2
3
4
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
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152198
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74354
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41442
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68040
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational 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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.