rs2407083

chr16-1202118-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.1668C>T(p.Pro556=) 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 1,546,556 control chromosomes in the GnomAD database, including 13,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 982 hom., cov: 34)

Exomes 𝑓: 0.13 ( 12616 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.57

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=-0.79).

BP6

Variant 16-1202118-C-T is Benign according to our data. Variant chr16-1202118-C-T is described in ClinVar as [Benign]. Clinvar id is 96002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1202118-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 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.1668C>T	p.Pro556=	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.1668C>T	p.Pro556=	synonymous_variant	9/35	1	NM_021098.3	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15373

AN:

152178

Hom.:

980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.0749

Gnomad AMR

AF:

0.0847

Gnomad ASJ

AF:

0.0625

Gnomad EAS

AF:

0.0633

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.115

AC:

16038

AN:

140046

Hom.:

1065

AF XY:

0.121

AC XY:

9197

AN XY:

75964

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.0587

Gnomad ASJ exome

AF:

0.0739

Gnomad EAS exome

AF:

0.0691

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.131

AC:

182907

AN:

1394260

Hom.:

12616

Cov.:

AF XY:

0.132

AC XY:

91019

AN XY:

687576

show subpopulations

Gnomad4 AFR exome

AF:

0.0335

Gnomad4 AMR exome

AF:

0.0619

Gnomad4 ASJ exome

AF:

0.0733

Gnomad4 EAS exome

AF:

0.0422

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.101

AC:

15369

AN:

152296

Hom.:

982

Cov.:

AF XY:

0.103

AC XY:

7634

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0375

Gnomad4 AMR

AF:

0.0846

Gnomad4 ASJ

AF:

0.0625

Gnomad4 EAS

AF:

0.0629

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.120

Hom.:

383

Bravo

AF:

0.0918

Asia WGS

AF:

0.111

AC:

388

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

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

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.62

Dann

Benign

0.80

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