rs543668710

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021098.3(CACNA1H):c.2604-4G>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 0.0000383 in 1,566,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Splicing: ADA: 0.00005757

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.36

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: G2P, Labcorp Genetics (formerly Invitae)

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-1206100-G-A is Benign according to our data. Variant chr16-1206100-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 460067.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.2604-4G>A		splice_region_variant, intron_variant	Intron 11 of 34	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CACNA1H	ENST00000348261.11 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000569107.6 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 33	1		ENSP00000454990.2
CACNA1H	ENST00000711493.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 33	1		ENSP00000455840.1
CACNA1H	ENST00000711450.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34	1		ENSP00000457555.2
CACNA1H	ENST00000638323.1 link	c.2565-4G>A	splice_region_variant, intron_variant	Intron 11 of 34	5		ENSP00000492267.1
CACNA1H	ENST00000562079.6 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 33	1		ENSP00000454581.2
CACNA1H	ENST00000711438.1 link	c.2565-4G>A	splice_region_variant, intron_variant	Intron 11 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 33	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1 link	n.*517-4G>A	splice_region_variant, intron_variant	Intron 11 of 34	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1 link	n.*2051-4G>A	splice_region_variant, intron_variant	Intron 10 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.2604-4G>A	splice_region_variant, intron_variant	Intron 11 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000482

AC:

AN:

186630

AF XY:

0.0000493

show subpopulations

Gnomad AFR exome

AF:

0.0000950

Gnomad AMR exome

AF:

0.0000342

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000382

AC:

AN:

1414582

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

699880

show subpopulations

African (AFR)

AF:

0.0000614

AC:

AN:

32560

American (AMR)

AF:

0.0000500

AC:

AN:

40028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25320

East Asian (EAS)

AF:

0.00

AC:

AN:

37518

South Asian (SAS)

AF:

0.000149

AC:

AN:

80570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5142

European-Non Finnish (NFE)

AF:

0.0000321

AC:

AN:

1091076

Other (OTH)

AF:

0.0000511

AC:

AN:

58680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000142

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV

Benign:1

Apr 19, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.22

(source)

DANN

Benign

0.72

PhyloP100

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000058

dbscSNV1_RF

Benign

0.0020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over