Variant 1-181785667-C-T 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.5680-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,281,290 control chromosomes in the GnomAD database, including 26,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3205 hom., cov: 32)

Exomes 𝑓: 0.20 ( 23211 hom. )

Consequence

CACNA1E
NM_001205293.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.444

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-181785667-C-T is Benign according to our data. Variant chr1-181785667-C-T is described in ClinVar as [Benign]. Clinvar id is 1262703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 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.5680-46C>T		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7 linkuse as main transcript	c.5680-46C>T	intron_variant	1	NM_001205293.3	ENSP00000356545	A2	Q15878-1
CACNA1E	ENST00000367570.6 linkuse as main transcript	c.5680-46C>T	intron_variant	1		ENSP00000356542	P4	Q15878-3
CACNA1E	ENST00000621791.4 linkuse as main transcript	c.5623-46C>T	intron_variant	1		ENSP00000481619	A2	Q15878-2
CACNA1E	ENST00000360108.7 linkuse as main transcript	c.5623-46C>T	intron_variant	5		ENSP00000353222	A2

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31021

AN:

152028

Hom.:

3201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.210

AC:

51448

AN:

245516

Hom.:

5753

AF XY:

0.215

AC XY:

28660

AN XY:

133412

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.197

AC:

221994

AN:

1129144

Hom.:

23211

Cov.:

AF XY:

0.201

AC XY:

115945

AN XY:

577752

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.204

AC:

31026

AN:

152146

Hom.:

3205

Cov.:

AF XY:

0.207

AC XY:

15396

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.187

Hom.:

5792

Bravo

AF:

0.202

Asia WGS

AF:

0.251

AC:

870

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 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.7

DANN

Benign

0.67

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