Variant rs704329 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.4494+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,603,568 control chromosomes in the GnomAD database, including 156,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11469 hom., cov: 32)

Exomes 𝑓: 0.44 ( 145461 hom. )

Consequence

CACNA1E
NM_001205293.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.442

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=-0.85).

BP6

Variant 1-181758137-G-A is Benign according to our data. Variant chr1-181758137-G-A is described in ClinVar as [Benign]. Clinvar id is 1292555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3 linkuse as main transcript	c.4494+26G>A		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7 linkuse as main transcript	c.4494+26G>A		intron_variant		1	NM_001205293.3	ENSP00000356545	A2	Q15878-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56239

AN:

151910

Hom.:

11455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.408

AC:

99866

AN:

244522

Hom.:

21241

AF XY:

0.417

AC XY:

55272

AN XY:

132432

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.399

Gnomad SAS exome

AF:

0.415

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.444

AC:

644319

AN:

1451540

Hom.:

145461

Cov.:

AF XY:

0.444

AC XY:

320164

AN XY:

721164

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.370

AC:

56277

AN:

152028

Hom.:

11469

Cov.:

AF XY:

0.372

AC XY:

27662

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.428

Gnomad4 FIN

AF:

0.464

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.433

Hom.:

20999

Bravo

AF:

0.350

Asia WGS

AF:

0.415

AC:

1441

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.85

CADD

Benign

0.70

DANN

Benign

0.45

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