rs3908956

Variant names:

• chr1-181631521-C-T
• rs3908956
• NM_001205293.3:c.952-19817C>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.952-19817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,060 control chromosomes in the GnomAD database, including 3,138 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 0.19 (3138 hom., cov: 33)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.952-19817C>T		intron	N/A	NP_001192222.1
	CACNA1E	NM_000721.4		c.952-19817C>T		intron	N/A	NP_000712.2
	CACNA1E	NM_001205294.2		c.952-19817C>T		intron	N/A	NP_001192223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.952-19817C>T		intron	N/A	ENSP00000356545.2
	CACNA1E	ENST00000360108.7	TSL:5	c.952-19817C>T		intron	N/A	ENSP00000353222.3
	CACNA1E	ENST00000367570.6	TSL:1	c.952-19817C>T		intron	N/A	ENSP00000356542.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29169 AN: 151942 Hom.: 3137 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.192 AC: 29173 AN: 152060 Hom.: 3138 Cov.: 33 AF XY: 0.191 AC XY: 14185 AN XY: 74336

African (AFR) AF: 0.257 AC: 10661 AN: 41456

American (AMR) AF: 0.184 AC: 2816 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3470

East Asian (EAS) AF: 0.0553 AC: 286 AN: 5174

South Asian (SAS) AF: 0.354 AC: 1700 AN: 4800

European-Finnish (FIN) AF: 0.122 AC: 1286 AN: 10582

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11188 AN: 67986

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.173 Hom.: 278

Bravo AF: 0.194

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.48
PhyloP100		-1.2
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: rs3908956; hg19: chr1-181600657;