Variant rs7540850 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001205293.3(CACNA1E):c.1316-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,610,998 control chromosomes in the GnomAD database, including 406,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 30270 hom., cov: 33)

Exomes 𝑓: 0.71 ( 376464 hom. )

Consequence

CACNA1E
NM_001205293.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.190

Variant links:

Genes affected

CACNA1E (HGNC:1392): (calcium voltage-gated channel subunit alpha1 E) Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CACNA1E 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=-0.81).

BP6

Variant 1-181717080-T-C is Benign according to our data. Variant chr1-181717080-T-C is described in ClinVar as [Benign]. Clinvar id is 1192683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3 linkuse as main transcript	c.1316-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7 linkuse as main transcript	c.1316-13T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001205293.3	A2	Q15878-1
CACNA1E	ENST00000367570.6 linkuse as main transcript	c.1316-13T>C	splice_polypyrimidine_tract_variant, intron_variant	1		P4	Q15878-3
CACNA1E	ENST00000621791.4 linkuse as main transcript	c.1316-13T>C	splice_polypyrimidine_tract_variant, intron_variant	1		A2	Q15878-2
CACNA1E	ENST00000360108.7 linkuse as main transcript	c.1316-13T>C	splice_polypyrimidine_tract_variant, intron_variant	5		A2

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

91163

AN:

152078

Hom.:

30249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.727

Gnomad OTH

AF:

0.599

GnomAD3 exomes

AF:

0.681

AC:

169553

AN:

248938

Hom.:

59333

AF XY:

0.688

AC XY:

92939

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.708

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.757

Gnomad NFE exome

AF:

0.726

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

AF:

0.714

AC:

1041334

AN:

1458802

Hom.:

376464

Cov.:

AF XY:

0.713

AC XY:

517811

AN XY:

725946

show subpopulations

Gnomad4 AFR exome

AF:

0.272

Gnomad4 AMR exome

AF:

0.651

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.788

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.756

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.695

GnomAD4 genome

AF:

0.599

AC:

91215

AN:

152196

Hom.:

30270

Cov.:

AF XY:

0.605

AC XY:

45020

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.661

Gnomad4 ASJ

AF:

0.712

Gnomad4 EAS

AF:

0.768

Gnomad4 SAS

AF:

0.655

Gnomad4 FIN

AF:

0.760

Gnomad4 NFE

AF:

0.727

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.689

Hom.:

38631

Bravo

AF:

0.577

Asia WGS

AF:

0.667

AC:

2321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2021	- -

Developmental and epileptic encephalopathy, 69

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.5

DANN

Benign

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

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