Variant rs28365123 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_021098.3(CACNA1H):c.2544C>A(p.Gly848=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 1,613,018 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 4 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.44

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 16-1205206-C-A is Benign according to our data. Variant chr16-1205206-C-A is described in ClinVar as [Benign]. Clinvar id is 460065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.44 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00513 (781/152288) while in subpopulation AFR AF= 0.0171 (710/41532). AF 95% confidence interval is 0.0161. There are 8 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 781 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1H	NM_021098.3 linkuse as main transcript	c.2544C>A	p.Gly848=	synonymous_variant	11/35	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.2544C>A	p.Gly848=	synonymous_variant	11/35	1	NM_021098.3	ENSP00000334198	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

780

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00125

AC:

311

AN:

248584

Hom.:

AF XY:

0.000910

AC XY:

123

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.000754

Gnomad ASJ exome

AF:

0.000998

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000977

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000564

AC:

824

AN:

1460730

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

369

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000693

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00513

AC:

781

AN:

152288

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

378

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000445

Hom.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.57

DANN

Benign

0.72

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

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