Variant rs28365124 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000348261.11(CACNA1H):c.4023G>A(p.Ala1341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,605,038 control chromosomes in the GnomAD database, including 3,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 249 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3083 hom. )

Consequence

CACNA1H
ENST00000348261.11 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.34

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-1210636-G-A is Benign according to our data. Variant chr16-1210636-G-A is described in ClinVar as [Benign]. Clinvar id is 585639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1210636-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1H	NM_021098.3 linkuse as main transcript	c.4023G>A	p.Ala1341=	synonymous_variant	20/35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11 linkuse as main transcript	c.4023G>A	p.Ala1341=	synonymous_variant	20/35	1	NM_021098.3	ENSP00000334198	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7160

AN:

152140

Hom.:

248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00948

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.0435

Gnomad ASJ

AF:

0.0916

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0669

Gnomad OTH

AF:

0.0569

GnomAD3 exomes

AF:

0.0553

AC:

13321

AN:

241058

Hom.:

478

AF XY:

0.0592

AC XY:

7814

AN XY:

131896

show subpopulations

Gnomad AFR exome

AF:

0.00881

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0925

Gnomad EAS exome

AF:

0.000393

Gnomad SAS exome

AF:

0.0880

Gnomad FIN exome

AF:

0.0520

Gnomad NFE exome

AF:

0.0653

Gnomad OTH exome

AF:

0.0663

GnomAD4 exome

AF:

0.0606

AC:

87993

AN:

1452780

Hom.:

3083

Cov.:

AF XY:

0.0618

AC XY:

44693

AN XY:

722948

show subpopulations

Gnomad4 AFR exome

AF:

0.00854

Gnomad4 AMR exome

AF:

0.0323

Gnomad4 ASJ exome

AF:

0.0936

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0865

Gnomad4 FIN exome

AF:

0.0520

Gnomad4 NFE exome

AF:

0.0629

Gnomad4 OTH exome

AF:

0.0607

GnomAD4 genome

AF:

0.0470

AC:

7161

AN:

152258

Hom.:

249

Cov.:

AF XY:

0.0457

AC XY:

3405

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00946

Gnomad4 AMR

AF:

0.0435

Gnomad4 ASJ

AF:

0.0916

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0833

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0669

Gnomad4 OTH

AF:

0.0558

Alfa

AF:

0.0646

Hom.:

101

Bravo

AF:

0.0419

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

EpiCase

AF:

0.0710

EpiControl

AF:

0.0722

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	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 2019	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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