rs369894677

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_021098.3(CACNA1H):c.1068C>T(p.Asn356Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,612,212 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22

Publications

1 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 16-1200520-C-T is Benign according to our data. Variant chr16-1200520-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 529669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.22 with no splicing effect.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CACNA1H	ENST00000348261.11 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 35	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000569107.6 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 34	1		ENSP00000454990.2
CACNA1H	ENST00000711493.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 34	1		ENSP00000455840.1
CACNA1H	ENST00000711450.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 35	1		ENSP00000457555.2
CACNA1H	ENST00000638323.1 link	c.1029C>T	p.Asn343Asn	synonymous_variant	Exon 7 of 35	5		ENSP00000492267.1
CACNA1H	ENST00000562079.6 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 34	1		ENSP00000454581.2
CACNA1H	ENST00000711438.1 link	c.1029C>T	p.Asn343Asn	synonymous_variant	Exon 7 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.1068C>T	p.Asn356Asn	synonymous_variant	Exon 7 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 34	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 35	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 35	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1 link	n.*515C>T		non_coding_transcript_exon_variant	Exon 6 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.1068C>T		non_coding_transcript_exon_variant	Exon 7 of 35			ENSP00000518777.1
CACNA1H	ENST00000711442.1 link	n.*515C>T		3_prime_UTR_variant	Exon 6 of 34			ENSP00000518758.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000689

AC:

AN:

246858

AF XY:

0.0000595

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

201

AN:

1460020

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

105

AN XY:

726300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.000134

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

51978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000160

AC:

178

AN:

1111700

Other (OTH)

AF:

0.000249

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000125

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41434

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000136

Hom.:

Bravo

AF:

0.000125

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Apr 23, 2022

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 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.42

CADD

Benign

4.3

(source)

DANN

Benign

0.83

PhyloP100

-1.2

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

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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