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GeneBe

16-1195062-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021098.3(CACNA1H):c.390C>T(p.Ser130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,605,332 control chromosomes in the GnomAD database, including 590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S130S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.035 ( 292 hom., cov: 29)
Exomes 𝑓: 0.0038 ( 298 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.01
Variant links:
Genes affected
CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. 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. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-1195062-C-T is Benign according to our data. Variant chr16-1195062-C-T is described in ClinVar as [Benign]. Clinvar id is 460099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1195062-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.01 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA1HNM_021098.3 linkuse as main transcriptc.390C>T p.Ser130= synonymous_variant 3/35 ENST00000348261.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA1HENST00000348261.11 linkuse as main transcriptc.390C>T p.Ser130= synonymous_variant 3/351 NM_021098.3 P4O95180-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0348
AC:
5230
AN:
150376
Hom.:
289
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0129
Gnomad ASJ
AF:
0.00116
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000211
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000649
Gnomad OTH
AF:
0.0247
GnomAD3 exomes
AF:
0.00919
AC:
2277
AN:
247862
Hom.:
119
AF XY:
0.00688
AC XY:
928
AN XY:
134836
show subpopulations
Gnomad AFR exome
AF:
0.125
Gnomad AMR exome
AF:
0.00716
Gnomad ASJ exome
AF:
0.00100
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000455
Gnomad OTH exome
AF:
0.00398
GnomAD4 exome
AF:
0.00384
AC:
5585
AN:
1454842
Hom.:
298
Cov.:
32
AF XY:
0.00335
AC XY:
2423
AN XY:
722958
show subpopulations
Gnomad4 AFR exome
AF:
0.129
Gnomad4 AMR exome
AF:
0.00783
Gnomad4 ASJ exome
AF:
0.00108
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000371
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.000260
Gnomad4 OTH exome
AF:
0.00900
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0349
AC:
5255
AN:
150490
Hom.:
292
Cov.:
29
AF XY:
0.0332
AC XY:
2441
AN XY:
73450
show subpopulations
Gnomad4 AFR
AF:
0.122
Gnomad4 AMR
AF:
0.0128
Gnomad4 ASJ
AF:
0.00116
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000211
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000649
Gnomad4 OTH
AF:
0.0244
Alfa
AF:
0.0196
Hom.:
106
Bravo
AF:
0.0398
Asia WGS
AF:
0.0100
AC:
37
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000830

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 03, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
1.4
Dann
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs59794024; hg19: chr16-1245062; API