rs9934839

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.1809A>G(p.Arg603Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,571,310 control chromosomes in the GnomAD database, including 194,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19495 hom., cov: 35)

Exomes 𝑓: 0.49 ( 174978 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.570

Publications

13 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=-0.73).

BP6

Variant 16-1202259-A-G is Benign according to our data. Variant chr16-1202259-A-G is described in ClinVar as Benign. ClinVar VariationId is 96003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 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.1809A>G	p.Arg603Arg	synonymous	Exon 9 of 35	NP_066921.2	O95180-1
	CACNA1H	NM_001005407.2		c.1809A>G	p.Arg603Arg	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.1809A>G	p.Arg603Arg	synonymous	Exon 9 of 35	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6	TSL:1	c.1809A>G	p.Arg603Arg	synonymous	Exon 9 of 34	ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1		c.1809A>G	p.Arg603Arg	synonymous	Exon 9 of 34	ENSP00000518778.1	A0AAA9YHG8

Frequencies

GnomAD3 genomes

AF:

0.494

AC:

75082

AN:

152050

Hom.:

19461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.418

AC:

74333

AN:

177792

AF XY:

0.419

show subpopulations

Gnomad AFR exome

AF:

0.594

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.536

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.488

AC:

692436

AN:

1419142

Hom.:

174978

Cov.:

AF XY:

0.483

AC XY:

339037

AN XY:

702244

show subpopulations

African (AFR)

AF:

0.588

AC:

18978

AN:

32260

American (AMR)

AF:

0.315

AC:

12256

AN:

38862

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8404

AN:

25426

East Asian (EAS)

AF:

0.0946

AC:

3494

AN:

36930

South Asian (SAS)

AF:

0.351

AC:

28319

AN:

80584

European-Finnish (FIN)

AF:

0.524

AC:

25194

AN:

48036

Middle Eastern (MID)

AF:

0.370

AC:

2109

AN:

5704

European-Non Finnish (NFE)

AF:

0.519

AC:

566732

AN:

1092518

Other (OTH)

AF:

0.458

AC:

26950

AN:

58822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

22312

44624

66936

89248

111560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16298

32596

48894

65192

81490

<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:

0.494

AC:

75158

AN:

152168

Hom.:

19495

Cov.:

AF XY:

0.488

AC XY:

36338

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.593

AC:

24604

AN:

41508

American (AMR)

AF:

0.372

AC:

5692

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1129

AN:

3468

East Asian (EAS)

AF:

0.127

AC:

656

AN:

5168

South Asian (SAS)

AF:

0.340

AC:

1645

AN:

4834

European-Finnish (FIN)

AF:

0.531

AC:

5630

AN:

10608

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34291

AN:

67964

Other (OTH)

AF:

0.462

AC:

977

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1980

3960

5940

7920

9900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.489

Hom.:

6571

Bravo

AF:

0.487

Asia WGS

AF:

0.254

AC:

887

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.1

(source)

DANN

Benign

0.42

PhyloP100

0.57

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