rs1054644

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021098.3(CACNA1H):c.6179G>A(p.Arg2060His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,483,932 control chromosomes in the GnomAD database, including 13,314 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 920 hom., cov: 35)

Exomes 𝑓: 0.13 ( 12394 hom. )

Consequence

CACNA1H
NM_021098.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.429

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051501095).

BP6

Variant 16-1220111-G-A is Benign according to our data. Variant chr16-1220111-G-A is described in ClinVar as [Benign]. Clinvar id is 96015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1220111-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.6179G>A	p.Arg2060His	missense_variant	Exon 35 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.6179G>A	p.Arg2060His	missense_variant	Exon 35 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.6161G>A	p.Arg2054His	missense_variant	Exon 33 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.6140G>A	p.Arg2047His	missense_variant	Exon 35 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000569107.5 link	c.2417G>A	p.Arg806His	missense_variant	Exon 17 of 17	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000564231.5 link	c.2369G>A	p.Arg790His	missense_variant	Exon 18 of 18	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000562079.5 link	c.2351G>A	p.Arg784His	missense_variant	Exon 17 of 17	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000639478.1 link	n.*1227G>A		non_coding_transcript_exon_variant	Exon 35 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*3997G>A		non_coding_transcript_exon_variant	Exon 35 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000639478.1 link	n.*1227G>A		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*3997G>A		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14328

AN:

152106

Hom.:

922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0265

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0848

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.0985

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.108

AC:

14677

AN:

135794

Hom.:

1013

AF XY:

0.116

AC XY:

8581

AN XY:

74262

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0775

Gnomad EAS exome

AF:

0.0216

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.0990

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.130

AC:

173665

AN:

1331708

Hom.:

12394

Cov.:

AF XY:

0.133

AC XY:

86695

AN XY:

651552

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.0507

Gnomad4 ASJ exome

AF:

0.0887

Gnomad4 EAS exome

AF:

0.0165

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.0941

AC:

14323

AN:

152224

Hom.:

920

Cov.:

AF XY:

0.0944

AC XY:

7022

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0263

Gnomad4 AMR

AF:

0.0737

Gnomad4 ASJ

AF:

0.0848

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.0985

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.0947

Alfa

AF:

0.107

Hom.:

444

TwinsUK

AF:

0.133

AC:

493

ALSPAC

AF:

0.132

AC:

510

ESP6500AA

AF:

0.0218

AC:

ESP6500EA

AF:

0.124

AC:

1025

ExAC

AF:

0.106

AC:

12587

Asia WGS

AF:

0.130

AC:

452

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 05, 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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

7.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.63

T;T;T;.

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.2

L;.;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.90

N;.;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.25

T;.;T;T

Sift4G

Benign

0.081

T;.;T;T

Polyphen

0.0020

B;.;B;B

Vest4

0.043

ClinPred

0.0014

GERP RS

0.24

Varity_R

0.043

gMVP

0.21

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