rs3856094

Variant names:

• chr1-181592647-C-T
• rs3856094
• NM_001205293.3:c.951+11871C>T

Variant summary

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

The NM_001205293.3(CACNA1E):​c.951+11871C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,068 control chromosomes in the GnomAD database, including 6,582 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 0.29 (6582 hom., cov: 31)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 7 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: Illumina, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.951+11871C>T		intron	N/A	NP_001192222.1	Q15878-1
	CACNA1E	NM_000721.4		c.951+11871C>T		intron	N/A	NP_000712.2	Q15878-3
	CACNA1E	NM_001205294.2		c.951+11871C>T		intron	N/A	NP_001192223.1	Q15878-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.951+11871C>T		intron	N/A	ENSP00000356545.2	Q15878-1
	CACNA1E	ENST00000360108.7	TSL:5	c.951+11871C>T		intron	N/A	ENSP00000353222.3	F8W9Z1
	CACNA1E	ENST00000367570.6	TSL:1	c.951+11871C>T		intron	N/A	ENSP00000356542.1	Q15878-3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44259 AN: 151948 Hom.: 6568 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.291 AC: 44297 AN: 152068 Hom.: 6582 Cov.: 31 AF XY: 0.290 AC XY: 21530 AN XY: 74346

African (AFR) AF: 0.255 AC: 10586 AN: 41500

American (AMR) AF: 0.354 AC: 5411 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1419 AN: 5176

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4808

European-Finnish (FIN) AF: 0.324 AC: 3417 AN: 10546

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20100 AN: 67970

Other (OTH) AF: 0.319 AC: 672 AN: 2106

Alfa AF: 0.301 Hom.: 11910

Bravo AF: 0.295

Asia WGS AF: 0.309 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		-0.19
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: rs3856094; hg19: chr1-181561783;