chr1-181367392-T-C

Variant names:

• chr1-181367392-T-C
• rs6658713
• ENST00000524607.6:c.-14-45741T>C

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.-14-45741T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,606 control chromosomes in the GnomAD database, including 8,896 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 0.33 (8896 hom., cov: 31)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926
• 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: 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524607.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000524607.6	TSL:5	c.-14-45741T>C		intron	N/A	ENSP00000432038.2	E9PIE8

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50240 AN: 151492 Hom.: 8864 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.332 AC: 50328 AN: 151606 Hom.: 8896 Cov.: 31 AF XY: 0.326 AC XY: 24179 AN XY: 74132

African (AFR) AF: 0.465 AC: 19191 AN: 41308

American (AMR) AF: 0.322 AC: 4908 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3468

East Asian (EAS) AF: 0.182 AC: 941 AN: 5174

South Asian (SAS) AF: 0.194 AC: 934 AN: 4804

European-Finnish (FIN) AF: 0.248 AC: 2580 AN: 10398

Middle Eastern (MID) AF: 0.266 AC: 77 AN: 290

European-Non Finnish (NFE) AF: 0.289 AC: 19636 AN: 67906

Other (OTH) AF: 0.314 AC: 661 AN: 2108

Alfa AF: 0.309 Hom.: 20177

Bravo AF: 0.346

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.83
PhyloP100		0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6658713; hg19: chr1-181336528;