rs377030217

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021098.3(CACNA1H):c.3846-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0018 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 intron

Scores

Splicing: ADA: 0.0002291

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.79

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-1210360-G-A is Benign according to our data. Variant chr16-1210360-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 585637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00238 (34/14286) while in subpopulation NFE AF = 0.00474 (27/5696). AF 95% confidence interval is 0.00334. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.3846-10G>A		intron_variant	Intron 18 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.3846-10G>A	intron_variant	Intron 18 of 34	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.3846-10G>A	intron_variant	Intron 18 of 33	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.3846-10G>A	intron_variant	Intron 18 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.3846-10G>A	intron_variant	Intron 18 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.3846-10G>A	intron_variant	Intron 18 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.3846-10G>A	intron_variant	Intron 18 of 34	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.3807-10G>A	intron_variant	Intron 18 of 34	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.3846-10G>A	intron_variant	Intron 18 of 33	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.3807-10G>A	intron_variant	Intron 18 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.3846-10G>A	intron_variant	Intron 18 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.3846-10G>A	intron_variant	Intron 18 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.3846-10G>A	intron_variant	Intron 18 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.3846-10G>A	intron_variant	Intron 18 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.3896-10G>A	intron_variant	Intron 18 of 33	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.3846-10G>A	intron_variant	Intron 18 of 34	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*1759-10G>A	intron_variant	Intron 18 of 34	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*3293-10G>A	intron_variant	Intron 17 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.3846-10G>A	intron_variant	Intron 18 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.3846-10G>A	intron_variant	Intron 18 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.3846-10G>A	intron_variant	Intron 18 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.3846-10G>A	intron_variant	Intron 18 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.3846-10G>A	intron_variant	Intron 18 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

AN:

14224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000441

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00421

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00474

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000724

AC:

AN:

40034

AF XY:

0.000905

show subpopulations

Gnomad AFR exome

AF:

0.000359

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000430

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00345

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00183

AC:

266

AN:

145028

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

133

AN XY:

78804

show subpopulations

African (AFR)

AF:

0.000261

AC:

AN:

3832

American (AMR)

AF:

0.00

AC:

AN:

8976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4312

East Asian (EAS)

AF:

0.000227

AC:

AN:

4398

South Asian (SAS)

AF:

0.0000460

AC:

AN:

21736

European-Finnish (FIN)

AF:

0.00282

AC:

AN:

6020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

930

European-Non Finnish (NFE)

AF:

0.00266

AC:

235

AN:

88432

Other (OTH)

AF:

0.00172

AC:

AN:

6392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.00238

AC:

AN:

14286

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

AN XY:

7612

show subpopulations

African (AFR)

AF:

0.000254

AC:

AN:

3938

American (AMR)

AF:

0.000440

AC:

AN:

2274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

240

East Asian (EAS)

AF:

0.00

AC:

AN:

312

South Asian (SAS)

AF:

0.00

AC:

AN:

304

European-Finnish (FIN)

AF:

0.00421

AC:

AN:

1188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00474

AC:

AN:

5696

Other (OTH)

AF:

0.00

AC:

AN:

270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.000246

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV

Benign:1

Oct 21, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 16, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

(source)

DANN

Benign

0.90

PhyloP100

-2.8

PromoterAI

-0.017

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.0

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over