rs9922076

chr16-1201803-C-T

Variant summary

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

The NM_021098.3(CACNA1H):c.1353C>T(p.Ser451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,590,818 control chromosomes in the GnomAD database, including 14,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 978 hom., cov: 34)

Exomes 𝑓: 0.13 ( 13033 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.54

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 16-1201803-C-T is Benign according to our data. Variant chr16-1201803-C-T is described in ClinVar as [Benign]. Clinvar id is 96000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1201803-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 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.1353C>T	p.Ser451=	synonymous_variant	9/35	ENST00000348261.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1H	ENST00000348261.11 linkuse as main transcript	c.1353C>T	p.Ser451=	synonymous_variant	9/35	1	NM_021098.3	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15371

AN:

152176

Hom.:

976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0856

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.0635

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.117

AC:

24578

AN:

209934

Hom.:

1608

AF XY:

0.123

AC XY:

13973

AN XY:

113812

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0579

Gnomad ASJ exome

AF:

0.0744

Gnomad EAS exome

AF:

0.0680

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.131

AC:

188797

AN:

1438524

Hom.:

13033

Cov.:

AF XY:

0.132

AC XY:

94446

AN XY:

713418

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.0740

Gnomad4 EAS exome

AF:

0.0429

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.101

AC:

15366

AN:

152294

Hom.:

978

Cov.:

AF XY:

0.102

AC XY:

7603

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.0855

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.0631

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.117

Hom.:

548

Bravo

AF:

0.0925

Asia WGS

AF:

0.112

AC:

391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 05, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 22, 2021	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

0.055

Dann

Benign

0.94

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