rs36117280

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.937A>G(p.Met313Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,605,316 control chromosomes in the GnomAD database, including 18,100 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1408 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16692 hom. )

Consequence

CACNA1H
NM_021098.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.365

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=0.0017673373).

BP6

Variant 16-1200389-A-G is Benign according to our data. Variant chr16-1200389-A-G is described in ClinVar as [Benign]. Clinvar id is 585657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1200389-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.937A>G	p.Met313Val	missense_variant	Exon 7 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.937A>G	p.Met313Val	missense_variant	Exon 7 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.937A>G	p.Met313Val	missense_variant	Exon 6 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.898A>G	p.Met300Val	missense_variant	Exon 7 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000639478.1 link	n.937A>G		non_coding_transcript_exon_variant	Exon 7 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.937A>G		non_coding_transcript_exon_variant	Exon 7 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19440

AN:

152186

Hom.:

1404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0847

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.0649

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.133

AC:

31097

AN:

233864

Hom.:

2234

AF XY:

0.140

AC XY:

17934

AN XY:

128240

show subpopulations

Gnomad AFR exome

AF:

0.0782

Gnomad AMR exome

AF:

0.0667

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.0664

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.149

AC:

216241

AN:

1453012

Hom.:

16692

Cov.:

AF XY:

0.150

AC XY:

108507

AN XY:

722448

show subpopulations

Gnomad4 AFR exome

AF:

0.0787

Gnomad4 AMR exome

AF:

0.0716

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0434

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.128

AC:

19462

AN:

152304

Hom.:

1408

Cov.:

AF XY:

0.129

AC XY:

9610

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0852

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.0644

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.139

Hom.:

1094

Bravo

AF:

0.120

TwinsUK

AF:

0.149

AC:

553

ALSPAC

AF:

0.154

AC:

593

ESP6500AA

AF:

0.0705

AC:

286

ESP6500EA

AF:

0.144

AC:

1201

ExAC

AF:

0.133

AC:

15899

Asia WGS

AF:

0.121

AC:

422

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 27, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

0.051

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

2.1

DANN

Benign

0.48

DEOGEN2

Benign

0.35

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.0082

T;T;T;.

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

-0.60

N;.;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.33

N;.;N;N

REVEL

Benign

0.27

Sift

Benign

0.67

T;.;T;T

Sift4G

Benign

1.0

T;.;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.18

ClinPred

0.00026

GERP RS

1.3

Varity_R

0.040

gMVP

0.76

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