rs1054645

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.6230G>A(p.Arg2077His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,523,120 control chromosomes in the GnomAD database, including 285,545 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 0.65 ( 32651 hom., cov: 35)

Exomes 𝑓: 0.60 ( 252894 hom. )

Consequence

CACNA1H
NM_021098.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.784

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=8.9449054E-7).

BP6

Variant 16-1220162-G-A is Benign according to our data. Variant chr16-1220162-G-A is described in ClinVar as [Benign]. Clinvar id is 96016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1220162-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.6230G>A	p.Arg2077His	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.6230G>A	p.Arg2077His	missense_variant	Exon 35 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.6212G>A	p.Arg2071His	missense_variant	Exon 33 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.6191G>A	p.Arg2064His	missense_variant	Exon 35 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000569107.5 link	c.2468G>A	p.Arg823His	missense_variant	Exon 17 of 17	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000564231.5 link	c.2420G>A	p.Arg807His	missense_variant	Exon 18 of 18	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000562079.5 link	c.2402G>A	p.Arg801His	missense_variant	Exon 17 of 17	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000639478.1 link	n.*1278G>A		non_coding_transcript_exon_variant	Exon 35 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*4048G>A		non_coding_transcript_exon_variant	Exon 35 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000639478.1 link	n.*1278G>A		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*4048G>A		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98790

AN:

152052

Hom.:

32623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.655

GnomAD3 exomes

AF:

0.657

AC:

109910

AN:

167372

Hom.:

36649

AF XY:

0.646

AC XY:

59692

AN XY:

92374

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.747

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.895

Gnomad SAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.701

Gnomad NFE exome

AF:

0.595

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.604

AC:

827558

AN:

1370950

Hom.:

252894

Cov.:

AF XY:

0.602

AC XY:

405972

AN XY:

674462

show subpopulations

Gnomad4 AFR exome

AF:

0.709

Gnomad4 AMR exome

AF:

0.735

Gnomad4 ASJ exome

AF:

0.697

Gnomad4 EAS exome

AF:

0.901

Gnomad4 SAS exome

AF:

0.561

Gnomad4 FIN exome

AF:

0.690

Gnomad4 NFE exome

AF:

0.582

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.650

AC:

98862

AN:

152170

Hom.:

32651

Cov.:

AF XY:

0.657

AC XY:

48845

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.699

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.876

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.585

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.607

Hom.:

47863

Bravo

AF:

0.659

TwinsUK

AF:

0.570

AC:

2113

ALSPAC

AF:

0.589

AC:

2269

ESP6500AA

AF:

0.728

AC:

2894

ESP6500EA

AF:

0.608

AC:

5031

ExAC

AF:

0.627

AC:

73990

Asia WGS

AF:

0.720

AC:

2501

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Nov 27, 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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.74

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.60

T;T;T;.

MetaRNN

Benign

8.9e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

N;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

0.45

N;.;N;N

REVEL

Benign

0.033

Sift

Benign

0.59

T;.;T;T

Sift4G

Benign

0.59

T;.;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.033

ClinPred

0.0018

GERP RS

0.76

Varity_R

0.022

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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