16-1195062-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021098.3(CACNA1H):c.390C>T(p.Ser130Ser) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.01

Publications

3 publications found

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]

CACNA1H Gene-Disease associations (from GenCC):

hyperaldosteronism, familial, type IV
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
childhood absence epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, childhood absence, susceptibility to, 6
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-1195062-C-T is Benign according to our data. Variant chr16-1195062-C-T is described in ClinVar as Benign. ClinVar VariationId is 460099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021098.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1H	NM_021098.3	MANE Select	c.390C>T	p.Ser130Ser	synonymous	Exon 3 of 35	NP_066921.2	O95180-1
	CACNA1H	NM_001005407.2		c.390C>T	p.Ser130Ser	synonymous	Exon 3 of 34	NP_001005407.1	O95180-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNA1H	ENST00000348261.11	TSL:1 MANE Select	c.390C>T	p.Ser130Ser	synonymous	Exon 3 of 35	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6	TSL:1	c.390C>T	p.Ser130Ser	synonymous	Exon 3 of 34	ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1		c.390C>T	p.Ser130Ser	synonymous	Exon 3 of 34	ENSP00000518778.1	A0AAA9YHG8

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5230

AN:

150376

Hom.:

289

Cov.:

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

GnomAD2 exomes

AF:

0.00919

AC:

2277

AN:

247862

AF XY:

0.00688

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 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.:

AF XY:

0.00335

AC XY:

2423

AN XY:

722958

show subpopulations

African (AFR)

AF:

0.129

AC:

4294

AN:

33332

American (AMR)

AF:

0.00783

AC:

349

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00108

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39444

South Asian (SAS)

AF:

0.000371

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52082

Middle Eastern (MID)

AF:

0.00922

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000260

AC:

288

AN:

1107496

Other (OTH)

AF:

0.00900

AC:

540

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

238

476

715

953

1191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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

AF:

0.0349

AC:

5255

AN:

150490

Hom.:

292

Cov.:

AF XY:

0.0332

AC XY:

2441

AN XY:

73450

show subpopulations

African (AFR)

AF:

0.122

AC:

4957

AN:

40774

American (AMR)

AF:

0.0128

AC:

194

AN:

15112

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.000211

AC:

AN:

4730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10262

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000649

AC:

AN:

67766

Other (OTH)

AF:

0.0244

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

215

431

646

862

1077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0188

Hom.:

117

Bravo

AF:

0.0398

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.4

(source)

DANN

Benign

0.91

PhyloP100

-4.0

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over