rs563361414

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021098.3(CACNA1H):c.5445+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000557 in 1,596,614 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00059 ( 8 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Splicing: ADA: 0.00004677

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.130

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-1218047-G-A is Benign according to our data. Variant chr16-1218047-G-A is described in ClinVar as Benign. ClinVar VariationId is 529693.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000289 (44/152348) while in subpopulation SAS AF = 0.00891 (43/4824). AF 95% confidence interval is 0.0068. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 44 AD gene.

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.5445+7G>A		splice_region intron	N/A	NP_066921.2	O95180-1
	CACNA1H	NM_001005407.2		c.5427+7G>A		splice_region intron	N/A	NP_001005407.1	O95180-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNA1H	ENST00000348261.11	TSL:1 MANE Select	c.5445+7G>A	splice_region intron	N/A	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6	TSL:1	c.5460+7G>A	splice_region intron	N/A	ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1		c.5463+7G>A	splice_region intron	N/A	ENSP00000518778.1	A0AAA9YHG8

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00891

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00127

AC:

285

AN:

224150

AF XY:

0.00169

show subpopulations

Gnomad AFR exome

AF:

0.0000784

Gnomad AMR exome

AF:

0.0000309

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00126

GnomAD4 exome

AF:

0.000586

AC:

846

AN:

1444266

Hom.:

Cov.:

AF XY:

0.000853

AC XY:

611

AN XY:

716366

show subpopulations

African (AFR)

AF:

0.0000905

AC:

AN:

33162

American (AMR)

AF:

0.0000233

AC:

AN:

42984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25772

East Asian (EAS)

AF:

0.00

AC:

AN:

38914

South Asian (SAS)

AF:

0.00940

AC:

787

AN:

83708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50948

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

1103424

Other (OTH)

AF:

0.000671

AC:

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

136

182

227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000289

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00891

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000171

Hom.:

Bravo

AF:

0.0000378

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CACNA1H-related disorder (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

(source)

DANN

Benign

0.78

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.0

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

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