chr1-181525392-C-G

Variant names:

• chr1-181525392-C-G
• rs594731
• NM_001205293.3:c.512+13882C>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.512+13882C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,258 control chromosomes in the GnomAD database, including 1,915 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 (1915 hom., cov: 33)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.512+13882C>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.512+13882C>G		intron_variant	Intron 3 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.512+13882C>G		intron_variant	Intron 3 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.512+13882C>G		intron_variant	Intron 3 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.512+13882C>G		intron_variant	Intron 3 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.947+13882C>G		intron_variant	Intron 5 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22839 AN: 152140 Hom.: 1914 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.150 AC: 22856 AN: 152258 Hom.: 1915 Cov.: 33 AF XY: 0.151 AC XY: 11246 AN XY: 74440

African (AFR) AF: 0.208 AC: 8632 AN: 41534

American (AMR) AF: 0.115 AC: 1753 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3472

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5190

South Asian (SAS) AF: 0.164 AC: 790 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1463 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9166 AN: 68028

Other (OTH) AF: 0.147 AC: 310 AN: 2116

Alfa AF: 0.140 Hom.: 205

Bravo AF: 0.148

Asia WGS AF: 0.0870 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.43
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: rs594731; hg19: chr1-181494528;