rs60526088

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.5778G>A(p.Ser1926Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,558,338 control chromosomes in the GnomAD database, including 1,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 321 hom., cov: 31)

Exomes 𝑓: 0.025 ( 711 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.27

Publications

6 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=-0.82).

BP6

Variant 16-1218542-G-A is Benign according to our data. Variant chr16-1218542-G-A is described in ClinVar as Benign. ClinVar VariationId is 446955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.5778G>A	p.Ser1926Ser	synonymous	Exon 33 of 35	NP_066921.2	O95180-1
	CACNA1H	NM_001005407.2		c.5760G>A	p.Ser1920Ser	synonymous	Exon 32 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.5778G>A	p.Ser1926Ser	synonymous	Exon 33 of 35	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6	TSL:1	c.5793G>A	p.Ser1931Ser	synonymous	Exon 32 of 34	ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1		c.5796G>A	p.Ser1932Ser	synonymous	Exon 32 of 34	ENSP00000518778.1	A0AAA9YHG8

Frequencies

GnomAD3 genomes

AF:

0.0462

AC:

7036

AN:

152130

Hom.:

313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0974

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.00782

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0355

AC:

5889

AN:

165988

AF XY:

0.0342

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0456

Gnomad ASJ exome

AF:

0.00704

Gnomad EAS exome

AF:

0.0916

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0248

AC:

34846

AN:

1406090

Hom.:

711

Cov.:

AF XY:

0.0247

AC XY:

17185

AN XY:

694384

show subpopulations

African (AFR)

AF:

0.112

AC:

3596

AN:

32036

American (AMR)

AF:

0.0440

AC:

1614

AN:

36670

Ashkenazi Jewish (ASJ)

AF:

0.00657

AC:

166

AN:

25270

East Asian (EAS)

AF:

0.0815

AC:

2969

AN:

36446

South Asian (SAS)

AF:

0.0378

AC:

3014

AN:

79726

European-Finnish (FIN)

AF:

0.0105

AC:

510

AN:

48378

Middle Eastern (MID)

AF:

0.0219

AC:

125

AN:

5704

European-Non Finnish (NFE)

AF:

0.0194

AC:

20989

AN:

1083496

Other (OTH)

AF:

0.0319

AC:

1863

AN:

58364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

2121

4242

6364

8485

10606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

938

1876

2814

3752

4690

<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:

0.0464

AC:

7067

AN:

152248

Hom.:

321

Cov.:

AF XY:

0.0458

AC XY:

3409

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.107

AC:

4455

AN:

41538

American (AMR)

AF:

0.0319

AC:

488

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.0978

AC:

505

AN:

5162

South Asian (SAS)

AF:

0.0418

AC:

202

AN:

4830

European-Finnish (FIN)

AF:

0.00782

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0180

AC:

1224

AN:

68004

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

331

663

994

1326

1657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0274

Hom.:

Bravo

AF:

0.0502

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

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)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.18

(source)

DANN

Benign

0.85

PhyloP100

-3.3

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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