NM_001205293.3:c.1056-24338C>T

Variant names:

• chr1-181686616-C-T
• rs3845441
• NM_001205293.3:c.1056-24338C>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.1056-24338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,166 control chromosomes in the GnomAD database, including 53,598 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 0.84 (53598 hom., cov: 31)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49
• 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: 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.863 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.1056-24338C>T		intron	N/A	NP_001192222.1	Q15878-1
	CACNA1E	NM_000721.4		c.1056-24338C>T		intron	N/A	NP_000712.2	Q15878-3
	CACNA1E	NM_001205294.2		c.1056-24338C>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.1056-24338C>T		intron	N/A	ENSP00000356545.2	Q15878-1
	CACNA1E	ENST00000360108.7	TSL:5	c.1056-24338C>T		intron	N/A	ENSP00000353222.3	F8W9Z1
	CACNA1E	ENST00000367570.6	TSL:1	c.1056-24338C>T		intron	N/A	ENSP00000356542.1	Q15878-3

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127521 AN: 152048 Hom.: 53550 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.839 AC: 127625 AN: 152166 Hom.: 53598 Cov.: 31 AF XY: 0.842 AC XY: 62606 AN XY: 74396

African (AFR) AF: 0.829 AC: 34401 AN: 41506

American (AMR) AF: 0.804 AC: 12307 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2914 AN: 3468

East Asian (EAS) AF: 0.814 AC: 4200 AN: 5160

South Asian (SAS) AF: 0.885 AC: 4270 AN: 4824

European-Finnish (FIN) AF: 0.861 AC: 9137 AN: 10608

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57656 AN: 67992

Other (OTH) AF: 0.808 AC: 1702 AN: 2106

Alfa AF: 0.835 Hom.: 16971

Bravo AF: 0.834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.056
DANN	Benign	0.50
PhyloP100		-3.5
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: rs3845441; hg19: chr1-181655752;