Variant 1-181755974-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000367573.7(CACNA1E):c.4008T>C(p.His1336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,612,618 control chromosomes in the GnomAD database, including 65,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8285 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57513 hom. )

Consequence

CACNA1E
ENST00000367573.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.472

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 1-181755974-T-C is Benign according to our data. Variant chr1-181755974-T-C is described in ClinVar as [Benign]. Clinvar id is 1192686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.472 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 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.4008T>C	p.His1336=	synonymous_variant	29/48	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.4008T>C	p.His1336=	synonymous_variant	29/48	1	NM_001205293.3	ENSP00000356545	A2	Q15878-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48551

AN:

151846

Hom.:

8266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.0658

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.323

GnomAD3 exomes

AF:

0.282

AC:

70281

AN:

248782

Hom.:

10915

AF XY:

0.283

AC XY:

38168

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.456

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.0584

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.275

AC:

401762

AN:

1460654

Hom.:

57513

Cov.:

AF XY:

0.278

AC XY:

201778

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.452

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.0594

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.320

AC:

48600

AN:

151964

Hom.:

8285

Cov.:

AF XY:

0.318

AC XY:

23596

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.0649

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.286

Hom.:

8408

Bravo

AF:

0.327

Asia WGS

AF:

0.210

AC:

728

AN:

3478

EpiCase

AF:

0.273

EpiControl

AF:

0.272

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.52

CADD

Benign

2.5

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