NM_021098.3:c.270C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021098.3(CACNA1H):c.270C>G(p.Arg90Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,404,994 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R90R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0035 ( 8 hom., cov: 30)

Exomes 𝑓: 0.0041 ( 79 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0260

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hyperaldosteronism, familial, type IV
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
childhood absence epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, childhood absence, susceptibility to, 6
Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-1154007-C-G is Benign according to our data. Variant chr16-1154007-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 460071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.026 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00353 (526/148996) while in subpopulation SAS AF = 0.0313 (146/4672). AF 95% confidence interval is 0.0271. There are 8 homozygotes in GnomAd4. There are 297 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 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.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

527

AN:

148924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000470

Gnomad AMI

AF:

0.00996

Gnomad AMR

AF:

0.00154

Gnomad ASJ

AF:

0.000581

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.00827

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.00349

Gnomad OTH

AF:

0.00389

GnomAD2 exomes

AF:

0.00962

AC:

695

AN:

72236

AF XY:

0.0126

show subpopulations

Gnomad AFR exome

AF:

0.000843

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.000471

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00666

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.00942

GnomAD4 exome

AF:

0.00407

AC:

5118

AN:

1255998

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

3092

AN XY:

618446

show subpopulations

African (AFR)

AF:

0.000315

AC:

AN:

25432

American (AMR)

AF:

0.00293

AC:

AN:

22498

Ashkenazi Jewish (ASJ)

AF:

0.000284

AC:

AN:

21162

East Asian (EAS)

AF:

0.0000381

AC:

AN:

26220

South Asian (SAS)

AF:

0.0320

AC:

2124

AN:

66354

European-Finnish (FIN)

AF:

0.00549

AC:

173

AN:

31526

Middle Eastern (MID)

AF:

0.0167

AC:

AN:

3706

European-Non Finnish (NFE)

AF:

0.00242

AC:

2442

AN:

1008702

Other (OTH)

AF:

0.00468

AC:

236

AN:

50398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

228

455

683

910

1138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00353

AC:

526

AN:

148996

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

297

AN XY:

72638

show subpopulations

African (AFR)

AF:

0.000468

AC:

AN:

40568

American (AMR)

AF:

0.00154

AC:

AN:

14916

Ashkenazi Jewish (ASJ)

AF:

0.000581

AC:

AN:

3444

East Asian (EAS)

AF:

0.000203

AC:

AN:

4916

South Asian (SAS)

AF:

0.0313

AC:

146

AN:

4672

European-Finnish (FIN)

AF:

0.00827

AC:

AN:

9920

Middle Eastern (MID)

AF:

0.00699

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00349

AC:

235

AN:

67296

Other (OTH)

AF:

0.00338

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00213

Asia WGS

AF:

0.00850

AC:

AN:

3306

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 08, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 07, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV

Benign:1

Aug 04, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Jan 20, 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

-0.60

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.026

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over