Variant rs2235634 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021098.3(CACNA1H):c.5244+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 0.137 in 1,608,102 control chromosomes in the GnomAD database, including 16,732 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 0.11 ( 1224 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15508 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Splicing: ADA: 0.0001214

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.60

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 16-1215600-G-A is Benign according to our data. Variant chr16-1215600-G-A is described in ClinVar as [Benign]. Clinvar id is 585649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1215600-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1H	NM_021098.3 linkuse as main transcript	c.5244+7G>A		splice_region_variant, intron_variant		ENST00000348261.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1H	ENST00000348261.11 linkuse as main transcript	c.5244+7G>A		splice_region_variant, intron_variant		1	NM_021098.3	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16714

AN:

152150

Hom.:

1225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0248

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.0964

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.138

AC:

32808

AN:

238482

Hom.:

2557

AF XY:

0.143

AC XY:

18635

AN XY:

130216

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.0791

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.140

AC:

203208

AN:

1455834

Hom.:

15508

Cov.:

AF XY:

0.142

AC XY:

102649

AN XY:

723924

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.0822

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.110

AC:

16707

AN:

152268

Hom.:

1224

Cov.:

AF XY:

0.111

AC XY:

8252

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0247

Gnomad4 AMR

AF:

0.0961

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.126

Hom.:

638

Bravo

AF:

0.103

Asia WGS

AF:

0.174

AC:

606

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over