NM_001205293.3:c.513-30801T>C

Variant names:

• chr1-181546965-T-C
• rs4652663
• NM_001205293.3:c.513-30801T>C

Variant summary

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

The NM_001205293.3(CACNA1E):​c.513-30801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,130 control chromosomes in the GnomAD database, including 2,618 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 0.15 (2618 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.513-30801T>C		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.513-30801T>C		intron_variant	Intron 3 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.513-30801T>C		intron_variant	Intron 3 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.513-30801T>C		intron_variant	Intron 3 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.513-30801T>C		intron_variant	Intron 3 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.948-30801T>C		intron_variant	Intron 5 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22987 AN: 152012 Hom.: 2611 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.151 AC: 23026 AN: 152130 Hom.: 2618 Cov.: 32 AF XY: 0.149 AC XY: 11049 AN XY: 74382

African (AFR) AF: 0.319 AC: 13210 AN: 41440

American (AMR) AF: 0.127 AC: 1949 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3468

East Asian (EAS) AF: 0.142 AC: 733 AN: 5174

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4830

European-Finnish (FIN) AF: 0.0799 AC: 847 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0775 AC: 5270 AN: 68002

Other (OTH) AF: 0.134 AC: 283 AN: 2114

Alfa AF: 0.100 Hom.: 1805

Bravo AF: 0.164

Asia WGS AF: 0.0980 AC: 339 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	2.8
DANN	Benign	0.41
PhyloP100		-0.12
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: rs4652663; hg19: chr1-181516101;