Variant 1-181772165-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000367573.7(CACNA1E):c.5073C>T(p.Asn1691=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,613,176 control chromosomes in the GnomAD database, including 50,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4795 hom., cov: 31)

Exomes 𝑓: 0.25 ( 45712 hom. )

Consequence

CACNA1E
ENST00000367573.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.92

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 1-181772165-C-T is Benign according to our data. Variant chr1-181772165-C-T is described in ClinVar as [Benign]. Clinvar id is 1232702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 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.5073C>T	p.Asn1691=	synonymous_variant	37/48	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.5073C>T	p.Asn1691=	synonymous_variant	37/48	1	NM_001205293.3	ENSP00000356545	A2	Q15878-1

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37841

AN:

151938

Hom.:

4790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.249

AC:

61992

AN:

249266

Hom.:

8326

AF XY:

0.252

AC XY:

34004

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.0584

Gnomad SAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.246

AC:

359483

AN:

1461120

Hom.:

45712

Cov.:

AF XY:

0.249

AC XY:

181137

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.0589

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.244

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.249

AC:

37864

AN:

152056

Hom.:

4795

Cov.:

AF XY:

0.249

AC XY:

18472

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.0646

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.237

Hom.:

8679

Bravo

AF:

0.250

Asia WGS

AF:

0.189

AC:

655

AN:

3478

EpiCase

AF:

0.249

EpiControl

AF:

0.245

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	clinical testing	GeneDx	Feb 28, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.38

DANN

Benign

0.84

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