rs748730819

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_021098.3(CACNA1H):c.1120-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,565,108 control chromosomes in the GnomAD database, including 6 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 4 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.255

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:

LOC124903623 (HGNC:):

LOC124903623 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 16-1200706-GC-G is Benign according to our data. Variant chr16-1200706-GC-G is described in ClinVar as [Benign]. Clinvar id is 529657.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00112 (171/152268) while in subpopulation AMR AF = 0.0109 (167/15298). AF 95% confidence interval is 0.00956. There are 2 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.1120-3delC		splice_region_variant, intron_variant	Intron 7 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.1120-9delC	intron_variant	Intron 7 of 34	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.1120-9delC	intron_variant	Intron 7 of 33	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.1120-9delC	intron_variant	Intron 7 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.1120-9delC	intron_variant	Intron 7 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.1120-9delC	intron_variant	Intron 7 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.1120-9delC	intron_variant	Intron 7 of 34	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.1081-9delC	intron_variant	Intron 7 of 34	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.1120-9delC	intron_variant	Intron 7 of 33	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.1081-9delC	intron_variant	Intron 7 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.1120-9delC	intron_variant	Intron 7 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.1120-9delC	intron_variant	Intron 7 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.1120-9delC	intron_variant	Intron 7 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.1120-9delC	intron_variant	Intron 7 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.1120-9delC	intron_variant	Intron 7 of 33	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.1120-9delC	intron_variant	Intron 7 of 34	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.1120-9delC	intron_variant	Intron 7 of 34	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*567-9delC	intron_variant	Intron 6 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.1120-9delC	intron_variant	Intron 7 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.1120-9delC	intron_variant	Intron 7 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.1120-9delC	intron_variant	Intron 7 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.1120-9delC	intron_variant	Intron 7 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.1120-9delC	intron_variant	Intron 7 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

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:

0.00

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000628

AC:

109

AN:

173676

AF XY:

0.000664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00398

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000823

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.000113

AC:

160

AN:

1412840

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

698664

show subpopulations

African (AFR)

AF:

0.0000624

AC:

AN:

32052

American (AMR)

AF:

0.00378

AC:

141

AN:

37256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25334

East Asian (EAS)

AF:

0.00

AC:

AN:

36620

South Asian (SAS)

AF:

0.0000984

AC:

AN:

81308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5508

European-Non Finnish (NFE)

AF:

0.00000276

AC:

AN:

1086920

Other (OTH)

AF:

0.000102

AC:

AN:

58580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00112

AC:

171

AN:

152268

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41536

American (AMR)

AF:

0.0109

AC:

167

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.00

Hom.:

Bravo

AF:

0.00137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Feb 02, 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

PhyloP100

0.26

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