Variant rs2280866 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001205293.3(CACNA1E):c.3423-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,317,528 control chromosomes in the GnomAD database, including 114,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 10880 hom., cov: 33)

Exomes 𝑓: 0.42 ( 104066 hom. )

Consequence

CACNA1E
NM_001205293.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-181737416-G-A is Benign according to our data. Variant chr1-181737416-G-A is described in ClinVar as [Benign]. Clinvar id is 1260688.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 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.3423-109G>A		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7 linkuse as main transcript	c.3423-109G>A		intron_variant		1	NM_001205293.3	A2	Q15878-1

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56012

AN:

151946

Hom.:

10861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.352

GnomAD4 exome

AF:

0.417

AC:

486471

AN:

1165466

Hom.:

104066

AF XY:

0.414

AC XY:

238337

AN XY:

576024

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.369

AC:

56070

AN:

152062

Hom.:

10880

Cov.:

AF XY:

0.364

AC XY:

27047

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.250

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.397

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.387

Hom.:

2316

Bravo

AF:

0.357

Asia WGS

AF:

0.264

AC:

922

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.81

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

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