dbSNP rs3845430: CACNA1E:c.434+15804G>A (chr1-181429384-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000524607.6(CACNA1E):c.434+15804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,938 control chromosomes in the GnomAD database, including 12,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12352 hom., cov: 31)

Consequence

CACNA1E
ENST00000524607.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

3 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:

LOC107985232 (HGNC:):

LOC107985232 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
LOC107985232	XR_007066763.1 link	n.1529G>A	non_coding_transcript_exon_variant	Exon 1 of 2
CACNA1E	XM_017002243.2 link	c.434+15804G>A	intron_variant	Intron 2 of 49	XP_016857732.1
CACNA1E	XM_017002244.2 link	c.434+15804G>A	intron_variant	Intron 2 of 49	XP_016857733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000524607.6 link	c.434+15804G>A		intron_variant	Intron 2 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60506

AN:

151820

Hom.:

12342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.399

AC:

60552

AN:

151938

Hom.:

12352

Cov.:

AF XY:

0.393

AC XY:

29161

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.457

AC:

18925

AN:

41422

American (AMR)

AF:

0.392

AC:

5998

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1546

AN:

3472

East Asian (EAS)

AF:

0.139

AC:

718

AN:

5158

South Asian (SAS)

AF:

0.265

AC:

1277

AN:

4816

European-Finnish (FIN)

AF:

0.363

AC:

3830

AN:

10558

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27055

AN:

67932

Other (OTH)

AF:

0.397

AC:

832

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1808

3615

5423

7230

9038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.407

Hom.:

1647

Bravo

AF:

0.402

Asia WGS

AF:

0.244

AC:

850

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.33

PhyloP100

-0.20

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over