rs8063574

Variant names:

Variant summary

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

The NM_021098.3(CACNA1H):c.3957T>C(p.Asp1319Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 1,611,656 control chromosomes in the GnomAD database, including 552,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 55890 hom., cov: 30)

Exomes 𝑓: 0.82 ( 496674 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.43

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=-0.78).

BP6

Variant 16-1210481-T-C is Benign according to our data. Variant chr16-1210481-T-C is described in ClinVar as [Benign]. Clinvar id is 96011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1210481-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.3957T>C	p.Asp1319Asp	synonymous_variant	Exon 19 of 35	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.3957T>C	p.Asp1319Asp	synonymous_variant	Exon 19 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.3957T>C	p.Asp1319Asp	synonymous_variant	Exon 18 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.3918T>C	p.Asp1306Asp	synonymous_variant	Exon 19 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000569107.5 link	c.180T>C	p.Asp60Asp	synonymous_variant	Exon 2 of 17	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000564231.5 link	c.180T>C	p.Asp60Asp	synonymous_variant	Exon 2 of 18	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000562079.5 link	c.180T>C	p.Asp60Asp	synonymous_variant	Exon 2 of 17	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000637236.2 link	n.320T>C		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.3957T>C		non_coding_transcript_exon_variant	Exon 19 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*1870T>C		non_coding_transcript_exon_variant	Exon 19 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000640028.1 link	n.*1870T>C		3_prime_UTR_variant	Exon 19 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.856

AC:

129918

AN:

151858

Hom.:

55831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.886

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.946

Gnomad FIN

AF:

0.860

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.801

Gnomad OTH

AF:

0.864

GnomAD3 exomes

AF:

0.860

AC:

212401

AN:

246952

Hom.:

91877

AF XY:

0.861

AC XY:

115829

AN XY:

134570

show subpopulations

Gnomad AFR exome

AF:

0.911

Gnomad AMR exome

AF:

0.872

Gnomad ASJ exome

AF:

0.878

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.940

Gnomad FIN exome

AF:

0.854

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.849

GnomAD4 exome

AF:

0.823

AC:

1201671

AN:

1459682

Hom.:

496674

Cov.:

AF XY:

0.826

AC XY:

599791

AN XY:

726178

show subpopulations

Gnomad4 AFR exome

AF:

0.919

Gnomad4 AMR exome

AF:

0.868

Gnomad4 ASJ exome

AF:

0.879

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.937

Gnomad4 FIN exome

AF:

0.852

Gnomad4 NFE exome

AF:

0.799

Gnomad4 OTH exome

AF:

0.844

GnomAD4 genome

AF:

0.856

AC:

130035

AN:

151974

Hom.:

55890

Cov.:

AF XY:

0.861

AC XY:

63912

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.911

Gnomad4 AMR

AF:

0.861

Gnomad4 ASJ

AF:

0.886

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.945

Gnomad4 FIN

AF:

0.860

Gnomad4 NFE

AF:

0.801

Gnomad4 OTH

AF:

0.867

Alfa

AF:

0.821

Hom.:

65872

Bravo

AF:

0.857

EpiCase

AF:

0.814

EpiControl

AF:

0.807

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epilepsy, childhood absence, susceptibility to, 6

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 03, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.3

DANN

Benign

0.62

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