16-1193557-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021098.3(CACNA1H):c.300-1415T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,336 control chromosomes in the GnomAD database, including 54,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.85 ( 54806 hom., cov: 38)

Consequence

CACNA1H
NM_021098.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.300-1415T>C		intron_variant	Intron 2 of 34	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.300-1415T>C	intron_variant	Intron 2 of 34	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.300-1415T>C	intron_variant	Intron 2 of 33	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.300-1415T>C	intron_variant	Intron 2 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.300-1415T>C	intron_variant	Intron 2 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.300-1415T>C	intron_variant	Intron 2 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.300-1415T>C	intron_variant	Intron 2 of 34	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.300-1415T>C	intron_variant	Intron 2 of 34	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.300-1415T>C	intron_variant	Intron 2 of 33	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.300-1415T>C	intron_variant	Intron 2 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.300-1415T>C	intron_variant	Intron 2 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.300-1415T>C	intron_variant	Intron 2 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.300-1415T>C	intron_variant	Intron 2 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.300-1415T>C	intron_variant	Intron 2 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.300-1415T>C	intron_variant	Intron 2 of 33	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.300-1415T>C	intron_variant	Intron 2 of 34	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.300-1415T>C	intron_variant	Intron 2 of 34	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.300-1415T>C	intron_variant	Intron 2 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.300-1415T>C	intron_variant	Intron 2 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.300-1415T>C	intron_variant	Intron 2 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.300-1415T>C	intron_variant	Intron 2 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.300-1415T>C	intron_variant	Intron 2 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.300-1415T>C	intron_variant	Intron 2 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.847

AC:

128884

AN:

152218

Hom.:

54753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.899

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.763

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.794

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.827

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.847

AC:

129001

AN:

152336

Hom.:

54806

Cov.:

AF XY:

0.849

AC XY:

63213

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.899

AC:

37397

AN:

41586

American (AMR)

AF:

0.866

AC:

13251

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.763

AC:

2646

AN:

3470

East Asian (EAS)

AF:

0.979

AC:

5075

AN:

5186

South Asian (SAS)

AF:

0.793

AC:

3827

AN:

4824

European-Finnish (FIN)

AF:

0.862

AC:

9154

AN:

10622

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.808

AC:

54942

AN:

68024

Other (OTH)

AF:

0.827

AC:

1748

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1072

2144

3216

4288

5360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.825

Hom.:

17575

Bravo

AF:

0.852

Asia WGS

AF:

0.875

AC:

3043

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.46

PhyloP100

-1.8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over