16-1207434-AG-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000348261.11(CACNA1H):c.3063+5delG variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000062 in 1,611,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CACNA1H
ENST00000348261.11 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.13

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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 16-1207434-AG-A is Benign according to our data. Variant chr16-1207434-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 529643.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.3063+9delG		intron_variant	Intron 14 of 34	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 33	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.3024+5delG	splice_region_variant, intron_variant	Intron 14 of 34	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 33	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.3024+5delG	splice_region_variant, intron_variant	Intron 14 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 33	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*976+5delG	splice_region_variant, intron_variant	Intron 14 of 34	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*2510+5delG	splice_region_variant, intron_variant	Intron 13 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.3063+5delG	splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000811

AC:

AN:

246506

AF XY:

0.00000744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460290

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.0000224

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111654

Other (OTH)

AF:

0.00

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41186

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67882

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

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

Oct 24, 2024

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

PhyloP100

4.1

Mutation Taster

=82/18

polymorphism

(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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16-1207434-AG-A

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