chr16-1218485-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021098.3(CACNA1H):c.5721C>T(p.Gly1907Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,551,744 control chromosomes in the GnomAD database, including 14,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 919 hom., cov: 34)

Exomes 𝑓: 0.13 ( 13304 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.129

Publications

10 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=-0.67).

BP6

Variant 16-1218485-C-T is Benign according to our data. Variant chr16-1218485-C-T is described in ClinVar as Benign. ClinVar VariationId is 585652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.129 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021098.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1H	NM_021098.3	MANE Select	c.5721C>T	p.Gly1907Gly	synonymous	Exon 33 of 35	NP_066921.2
	CACNA1H	NM_001005407.2		c.5703C>T	p.Gly1901Gly	synonymous	Exon 32 of 34	NP_001005407.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CACNA1H	ENST00000348261.11	TSL:1 MANE Select	c.5721C>T	p.Gly1907Gly	synonymous	Exon 33 of 35	ENSP00000334198.7
CACNA1H	ENST00000569107.6	TSL:1	c.5736C>T	p.Gly1912Gly	synonymous	Exon 32 of 34	ENSP00000454990.2
CACNA1H	ENST00000711493.1		c.5739C>T	p.Gly1913Gly	synonymous	Exon 32 of 34	ENSP00000518778.1

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14327

AN:

152052

Hom.:

921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0739

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.0230

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.0986

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0947

GnomAD2 exomes

AF:

0.117

AC:

18331

AN:

156264

AF XY:

0.129

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.0928

Gnomad EAS exome

AF:

0.0243

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.131

AC:

183551

AN:

1399574

Hom.:

13304

Cov.:

AF XY:

0.135

AC XY:

93022

AN XY:

690564

show subpopulations

African (AFR)

AF:

0.0235

AC:

744

AN:

31684

American (AMR)

AF:

0.0566

AC:

2030

AN:

35888

Ashkenazi Jewish (ASJ)

AF:

0.0915

AC:

2305

AN:

25184

East Asian (EAS)

AF:

0.0171

AC:

612

AN:

35862

South Asian (SAS)

AF:

0.236

AC:

18759

AN:

79332

European-Finnish (FIN)

AF:

0.107

AC:

5116

AN:

47858

Middle Eastern (MID)

AF:

0.0924

AC:

525

AN:

5680

European-Non Finnish (NFE)

AF:

0.136

AC:

146533

AN:

1079984

Other (OTH)

AF:

0.119

AC:

6927

AN:

58102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

10005

20009

30014

40018

50023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5354

10708

16062

21416

26770

<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:

0.0941

AC:

14321

AN:

152170

Hom.:

919

Cov.:

AF XY:

0.0944

AC XY:

7020

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0273

AC:

1135

AN:

41536

American (AMR)

AF:

0.0738

AC:

1130

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0844

AC:

293

AN:

3470

East Asian (EAS)

AF:

0.0227

AC:

117

AN:

5158

South Asian (SAS)

AF:

0.245

AC:

1178

AN:

4808

European-Finnish (FIN)

AF:

0.0986

AC:

1045

AN:

10600

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9109

AN:

67978

Other (OTH)

AF:

0.0942

AC:

199

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

632

1265

1897

2530

3162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.118

Hom.:

385

Bravo

AF:

0.0842

Asia WGS

AF:

0.127

AC:

443

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.50

(source)

DANN

Benign

0.73

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over