rs704329

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 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 -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 VariationId 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 rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3 link	c.4494+26G>A		intron_variant	Intron 31 of 47	ENST00000367573.7	NP_001192222.1	Q15878-1Q59FG1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1E	ENST00000367573.7 link	c.4494+26G>A	intron_variant	Intron 31 of 47	1	NM_001205293.3	ENSP00000356545.2	Q15878-1
CACNA1E	ENST00000360108.7 link	c.4437+26G>A	intron_variant	Intron 30 of 46	5		ENSP00000353222.3	F8W9Z1
CACNA1E	ENST00000367570.6 link	c.4494+26G>A	intron_variant	Intron 31 of 46	1		ENSP00000356542.1	Q15878-3
CACNA1E	ENST00000621791.4 link	c.4437+26G>A	intron_variant	Intron 30 of 45	1		ENSP00000481619.1	Q15878-2

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

GnomAD2 exomes

AF:

0.408

AC:

99866

AN:

244522

AF XY:

0.417

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 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

African (AFR)

AF:

0.177

AC:

5903

AN:

33286

American (AMR)

AF:

0.319

AC:

14151

AN:

44382

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

10734

AN:

25878

East Asian (EAS)

AF:

0.441

AC:

17433

AN:

39500

South Asian (SAS)

AF:

0.415

AC:

35478

AN:

85560

European-Finnish (FIN)

AF:

0.462

AC:

24572

AN:

53186

Middle Eastern (MID)

AF:

0.357

AC:

1797

AN:

5030

European-Non Finnish (NFE)

AF:

0.461

AC:

509451

AN:

1104814

Other (OTH)

AF:

0.414

AC:

24800

AN:

59904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

16254

32507

48761

65014

81268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15190

30380

45570

60760

75950

<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:

0.370

AC:

56277

AN:

152028

Hom.:

11469

Cov.:

AF XY:

0.372

AC XY:

27662

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.190

AC:

7886

AN:

41488

American (AMR)

AF:

0.348

AC:

5317

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1481

AN:

3470

East Asian (EAS)

AF:

0.422

AC:

2179

AN:

5158

South Asian (SAS)

AF:

0.428

AC:

2062

AN:

4818

European-Finnish (FIN)

AF:

0.464

AC:

4891

AN:

10546

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.459

AC:

31225

AN:

67962

Other (OTH)

AF:

0.357

AC:

753

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1744

3488

5231

6975

8719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.422

Hom.:

29452

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

Mar 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.70

(source)

DANN

Benign

0.45

PhyloP100

-0.44

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