chr16-1200559-T-C

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.1107T>C(p.Ile369Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,611,322 control chromosomes in the GnomAD database, including 150,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14162 hom., cov: 33)

Exomes 𝑓: 0.42 ( 136779 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.69

Publications

17 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: Labcorp Genetics (formerly Invitae), G2P
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CACNA1H links:

LOC124903623 (HGNC:):

LOC124903623 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=-0.82).

BP6

Variant 16-1200559-T-C is Benign according to our data. Variant chr16-1200559-T-C is described in ClinVar as Benign. ClinVar VariationId is 166755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 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.1107T>C	p.Ile369Ile	synonymous	Exon 7 of 35	NP_066921.2	O95180-1
	CACNA1H	NM_001005407.2		c.1107T>C	p.Ile369Ile	synonymous	Exon 7 of 34	NP_001005407.1	O95180-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNA1H	ENST00000348261.11	TSL:1 MANE Select	c.1107T>C	p.Ile369Ile	synonymous	Exon 7 of 35	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6	TSL:1	c.1107T>C	p.Ile369Ile	synonymous	Exon 7 of 34	ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1		c.1107T>C	p.Ile369Ile	synonymous	Exon 7 of 34	ENSP00000518778.1	A0AAA9YHG8

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

64020

AN:

151904

Hom.:

14133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.385

GnomAD2 exomes

AF:

0.370

AC:

90696

AN:

245158

AF XY:

0.371

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.424

AC:

619188

AN:

1459300

Hom.:

136779

Cov.:

AF XY:

0.420

AC XY:

304849

AN XY:

725992

show subpopulations

African (AFR)

AF:

0.487

AC:

16299

AN:

33462

American (AMR)

AF:

0.270

AC:

12087

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6554

AN:

26100

East Asian (EAS)

AF:

0.0844

AC:

3350

AN:

39690

South Asian (SAS)

AF:

0.313

AC:

26969

AN:

86238

European-Finnish (FIN)

AF:

0.491

AC:

25321

AN:

51594

Middle Eastern (MID)

AF:

0.271

AC:

1563

AN:

5764

European-Non Finnish (NFE)

AF:

0.453

AC:

503390

AN:

1111448

Other (OTH)

AF:

0.392

AC:

23655

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19503

39006

58508

78011

97514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15000

30000

45000

60000

75000

<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:

0.422

AC:

64089

AN:

152022

Hom.:

14162

Cov.:

AF XY:

0.417

AC XY:

31000

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.492

AC:

20410

AN:

41446

American (AMR)

AF:

0.308

AC:

4703

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

855

AN:

3468

East Asian (EAS)

AF:

0.115

AC:

595

AN:

5166

South Asian (SAS)

AF:

0.299

AC:

1444

AN:

4826

European-Finnish (FIN)

AF:

0.497

AC:

5260

AN:

10580

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29658

AN:

67940

Other (OTH)

AF:

0.380

AC:

800

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1896

3793

5689

7586

9482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.398

Hom.:

7728

Bravo

AF:

0.411

Asia WGS

AF:

0.229

AC:

796

AN:

3478

EpiCase

AF:

0.404

EpiControl

AF:

0.408

ClinVar

ClinVar submissions

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)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.79

PhyloP100

-2.7

Mutation Taster

=95/5

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