rs2280869

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001205293.3(CACNA1E):c.*216T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 448,958 control chromosomes in the GnomAD database, including 2,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 711 hom., cov: 33)

Exomes 𝑓: 0.084 ( 1781 hom. )

Consequence

CACNA1E
NM_001205293.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.345

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 69
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

CACNA1E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-181799050-T-C is Benign according to our data. Variant chr1-181799050-T-C is described in ClinVar as Benign. ClinVar VariationId is 1228100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3 link	c.*216T>C		3_prime_UTR_variant	Exon 48 of 48	ENST00000367573.7	NP_001192222.1	Q15878-1Q59FG1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1E	ENST00000367573.7 link	c.*216T>C	3_prime_UTR_variant	Exon 48 of 48	1	NM_001205293.3	ENSP00000356545.2	Q15878-1
CACNA1E	ENST00000367570.6 link	c.*216T>C	3_prime_UTR_variant	Exon 47 of 47	1		ENSP00000356542.1	Q15878-3
CACNA1E	ENST00000621791.4 link	c.*216T>C	3_prime_UTR_variant	Exon 46 of 46	1		ENSP00000481619.1	Q15878-2
CACNA1E	ENST00000360108.7 link	c.*216T>C	downstream_gene_variant		5		ENSP00000353222.3	F8W9Z1

Frequencies

GnomAD3 genomes

AF:

0.0802

AC:

12203

AN:

152164

Hom.:

706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0590

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0653

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0538

Gnomad OTH

AF:

0.0717

GnomAD4 exome

AF:

0.0840

AC:

24932

AN:

296676

Hom.:

1781

Cov.:

AF XY:

0.0844

AC XY:

12737

AN XY:

150888

show subpopulations

African (AFR)

AF:

0.0751

AC:

664

AN:

8838

American (AMR)

AF:

0.159

AC:

1659

AN:

10410

Ashkenazi Jewish (ASJ)

AF:

0.0659

AC:

672

AN:

10196

East Asian (EAS)

AF:

0.304

AC:

7321

AN:

24086

South Asian (SAS)

AF:

0.115

AC:

1324

AN:

11476

European-Finnish (FIN)

AF:

0.0565

AC:

1269

AN:

22464

Middle Eastern (MID)

AF:

0.0414

AC:

AN:

1472

European-Non Finnish (NFE)

AF:

0.0554

AC:

10481

AN:

189076

Other (OTH)

AF:

0.0794

AC:

1481

AN:

18658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1012

2024

3035

4047

5059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0801

AC:

12203

AN:

152282

Hom.:

711

Cov.:

AF XY:

0.0851

AC XY:

6339

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0748

AC:

3111

AN:

41568

American (AMR)

AF:

0.143

AC:

2191

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

205

AN:

3472

East Asian (EAS)

AF:

0.288

AC:

1483

AN:

5146

South Asian (SAS)

AF:

0.114

AC:

552

AN:

4824

European-Finnish (FIN)

AF:

0.0653

AC:

693

AN:

10620

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0538

AC:

3659

AN:

68032

Other (OTH)

AF:

0.0705

AC:

149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

578

1157

1735

2314

2892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0619

Hom.:

419

Bravo

AF:

0.0868

Asia WGS

AF:

0.179

AC:

624

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over