Variant rs377030217 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021098.3(CACNA1H):c.3846-10G>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002291

Clinical Significance

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

Conservation

PhyloP100: -2.79

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1H	NM_021098.3 linkuse as main transcript	c.3846-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000348261.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1H	ENST00000348261.11 linkuse as main transcript	c.3846-10G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021098.3	P4	O95180-1

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

GnomAD3 exomes

AF:

0.000724

AC:

AN:

40034

Hom.:

AF XY:

0.000905

AC XY:

AN XY:

21006

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 SAS 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

Gnomad4 AFR exome

AF:

0.000261

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0000460

Gnomad4 FIN exome

AF:

0.00282

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00238

AC:

AN:

14286

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

AN XY:

7612

show subpopulations

Gnomad4 AFR

AF:

0.000254

Gnomad4 AMR

AF:

0.000440

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00421

Gnomad4 NFE

AF:

0.00474

Gnomad4 OTH

AF:

0.00

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

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 21, 2021

- -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

DANN

Benign

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over