rs9922076

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1353C>T(p.Ser451Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,590,818 control chromosomes in the GnomAD database, including 14,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 978 hom., cov: 34)

Exomes 𝑓: 0.13 ( 13033 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -5.54

Publications

11 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:

LOC124903623 (HGNC:):

LOC124903623 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=-0.74).

BP6

Variant 16-1201803-C-T is Benign according to our data. Variant chr16-1201803-C-T is described in ClinVar as Benign. ClinVar VariationId is 96000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 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.1353C>T	p.Ser451Ser	synonymous	Exon 9 of 35	NP_066921.2	O95180-1
	CACNA1H	NM_001005407.2		c.1353C>T	p.Ser451Ser	synonymous	Exon 9 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.1353C>T	p.Ser451Ser	synonymous	Exon 9 of 35	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6	TSL:1	c.1353C>T	p.Ser451Ser	synonymous	Exon 9 of 34	ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1		c.1353C>T	p.Ser451Ser	synonymous	Exon 9 of 34	ENSP00000518778.1	A0AAA9YHG8

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15371

AN:

152176

Hom.:

976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0856

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.0635

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.117

AC:

24578

AN:

209934

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0579

Gnomad ASJ exome

AF:

0.0744

Gnomad EAS exome

AF:

0.0680

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.131

AC:

188797

AN:

1438524

Hom.:

13033

Cov.:

AF XY:

0.132

AC XY:

94446

AN XY:

713418

show subpopulations

African (AFR)

AF:

0.0334

AC:

1103

AN:

33030

American (AMR)

AF:

0.0601

AC:

2480

AN:

41244

Ashkenazi Jewish (ASJ)

AF:

0.0740

AC:

1900

AN:

25688

East Asian (EAS)

AF:

0.0429

AC:

1656

AN:

38590

South Asian (SAS)

AF:

0.156

AC:

12895

AN:

82832

European-Finnish (FIN)

AF:

0.147

AC:

7390

AN:

50346

Middle Eastern (MID)

AF:

0.0946

AC:

530

AN:

5604

European-Non Finnish (NFE)

AF:

0.140

AC:

153701

AN:

1101570

Other (OTH)

AF:

0.120

AC:

7142

AN:

59620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

11187

22374

33562

44749

55936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5506

11012

16518

22024

27530

<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:

0.101

AC:

15366

AN:

152294

Hom.:

978

Cov.:

AF XY:

0.102

AC XY:

7603

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0381

AC:

1583

AN:

41568

American (AMR)

AF:

0.0855

AC:

1308

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

219

AN:

3470

East Asian (EAS)

AF:

0.0631

AC:

327

AN:

5184

South Asian (SAS)

AF:

0.151

AC:

730

AN:

4834

European-Finnish (FIN)

AF:

0.152

AC:

1614

AN:

10618

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9250

AN:

67996

Other (OTH)

AF:

0.112

AC:

236

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

743

1486

2228

2971

3714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.117

Hom.:

548

Bravo

AF:

0.0925

Asia WGS

AF:

0.112

AC:

391

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

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

-0.74

CADD

Benign

0.055

(source)

DANN

Benign

0.94

PhyloP100

-5.5

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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