rs3905011

Variant names:

• chr1-181576458-A-G
• rs3905011
• NM_001205293.3:c.513-1308A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205293.3(CACNA1E):​c.513-1308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,100 control chromosomes in the GnomAD database, including 25,776 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 0.58 (25776 hom., cov: 33)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 5 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.513-1308A>G		intron_variant	Intron 3 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.513-1308A>G		intron_variant	Intron 3 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.513-1308A>G		intron_variant	Intron 3 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.513-1308A>G		intron_variant	Intron 3 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.513-1308A>G		intron_variant	Intron 3 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.948-1308A>G		intron_variant	Intron 5 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87939 AN: 151980 Hom.: 25744 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.579 AC: 88023 AN: 152100 Hom.: 25776 Cov.: 33 AF XY: 0.584 AC XY: 43409 AN XY: 74370

African (AFR) AF: 0.531 AC: 22026 AN: 41484

American (AMR) AF: 0.557 AC: 8518 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3610 AN: 5172

South Asian (SAS) AF: 0.596 AC: 2877 AN: 4826

European-Finnish (FIN) AF: 0.583 AC: 6164 AN: 10564

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40617 AN: 67984

Other (OTH) AF: 0.553 AC: 1163 AN: 2104

Alfa AF: 0.583 Hom.: 4732

Bravo AF: 0.573

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.22
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3905011; hg19: chr1-181545594;