rs188397970

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021098.3(CACNA1H):c.1120-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,565,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Splicing: ADA: 0.003379

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

175096

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000849

AC:

AN:

1413188

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

698766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32040

American (AMR)

AF:

0.00

AC:

AN:

37222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25330

East Asian (EAS)

AF:

0.00

AC:

AN:

36634

South Asian (SAS)

AF:

0.0000862

AC:

AN:

81204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.00000460

AC:

AN:

1087232

Other (OTH)

AF:

0.00

AC:

AN:

58598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

(source)

DANN

Benign

0.29

PhyloP100

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0034

dbscSNV1_RF

Benign

0.068

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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