rs545116263

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS2

The NM_021098.3(CACNA1H):c.4223+8delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,440,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0150

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 16-1210973-TG-T is Benign according to our data. Variant chr16-1210973-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1918960.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.4223+8delG		splice_region_variant, intron_variant	Intron 21 of 34	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CACNA1H	ENST00000348261.11 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000569107.6 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 33	1		ENSP00000454990.2
CACNA1H	ENST00000711493.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 33	1		ENSP00000455840.1
CACNA1H	ENST00000711450.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34	1		ENSP00000457555.2
CACNA1H	ENST00000638323.1 link	c.4184+3delG	splice_region_variant, intron_variant	Intron 21 of 34	5		ENSP00000492267.1
CACNA1H	ENST00000562079.6 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 33	1		ENSP00000454581.2
CACNA1H	ENST00000711438.1 link	c.4184+3delG	splice_region_variant, intron_variant	Intron 21 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.*193+3delG	splice_region_variant, intron_variant	Intron 21 of 33	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1 link	n.*2136+3delG	splice_region_variant, intron_variant	Intron 21 of 34	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1 link	n.*3670+3delG	splice_region_variant, intron_variant	Intron 20 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.4223+3delG	splice_region_variant, intron_variant	Intron 21 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000422

AC:

AN:

236998

AF XY:

0.00000771

show subpopulations

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:

0.0000754

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1440526

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

715882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33294

American (AMR)

AF:

0.00

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.00

AC:

AN:

39518

South Asian (SAS)

AF:

0.00

AC:

AN:

85950

European-Finnish (FIN)

AF:

0.0000249

AC:

AN:

40192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4374

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1106876

Other (OTH)

AF:

0.00

AC:

AN:

59804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Apr 20, 2022

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

-0.015

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over