1-181772165-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001205293.3(CACNA1E):c.5073C>T(p.Asn1691Asn) 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
NM_001205293.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.92

Publications

21 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 -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 VariationId 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 rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3 link	c.5073C>T	p.Asn1691Asn	synonymous_variant	Exon 37 of 48	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CACNA1E	ENST00000367573.7 link	c.5073C>T	p.Asn1691Asn	synonymous_variant	Exon 37 of 48	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7 link	c.5016C>T	p.Asn1672Asn	synonymous_variant	Exon 36 of 47	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6 link	c.5073C>T	p.Asn1691Asn	synonymous_variant	Exon 37 of 47	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4 link	c.5016C>T	p.Asn1672Asn	synonymous_variant	Exon 36 of 46	1		ENSP00000481619.1

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

GnomAD2 exomes

AF:

0.249

AC:

61992

AN:

249266

AF XY:

0.252

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 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

African (AFR)

AF:

0.258

AC:

8631

AN:

33464

American (AMR)

AF:

0.295

AC:

13169

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

5246

AN:

26126

East Asian (EAS)

AF:

0.0589

AC:

2340

AN:

39700

South Asian (SAS)

AF:

0.343

AC:

29565

AN:

86202

European-Finnish (FIN)

AF:

0.239

AC:

12764

AN:

53388

Middle Eastern (MID)

AF:

0.326

AC:

1878

AN:

5766

European-Non Finnish (NFE)

AF:

0.244

AC:

270839

AN:

1111418

Other (OTH)

AF:

0.249

AC:

15051

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

14449

28899

43348

57798

72247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9200

18400

27600

36800

46000

<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:

0.249

AC:

37864

AN:

152056

Hom.:

4795

Cov.:

AF XY:

0.249

AC XY:

18472

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.259

AC:

10730

AN:

41476

American (AMR)

AF:

0.278

AC:

4250

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

623

AN:

3468

East Asian (EAS)

AF:

0.0646

AC:

335

AN:

5184

South Asian (SAS)

AF:

0.334

AC:

1601

AN:

4790

European-Finnish (FIN)

AF:

0.241

AC:

2551

AN:

10586

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.249

AC:

16899

AN:

67970

Other (OTH)

AF:

0.264

AC:

556

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1420

2840

4261

5681

7101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.241

Hom.:

13155

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 28, 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

- -

Developmental and epileptic encephalopathy, 69

Benign:1

Apr 11, 2023

Genome-Nilou Lab

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

-0.40

CADD

Benign

0.38

(source)

DANN

Benign

0.84

PhyloP100

-1.9

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