ENST00000524607.6:c.435-25970C>T

Variant names:

• chr1-181457774-C-T
• rs2332267
• ENST00000524607.6:c.435-25970C>T

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.435-25970C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,242 control chromosomes in the GnomAD database, including 819 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 0.094 (819 hom., cov: 33)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 7 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

ENSG00000297520 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.435-25970C>T		intron_variant	Intron 2 of 49		XP_016857732.1
CACNA1E	XM_017002244.2	c.435-25970C>T		intron_variant	Intron 2 of 49		XP_016857733.1
CACNA1E	XM_017002251.1	c.435-25970C>T		intron_variant	Intron 2 of 49		XP_016857740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000524607.6	c.435-25970C>T		intron_variant	Intron 2 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14238 AN: 152124 Hom.: 822 Cov.: 33

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0977

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

GnomAD4 genome AF: 0.0935 AC: 14235 AN: 152242 Hom.: 819 Cov.: 33 AF XY: 0.0964 AC XY: 7174 AN XY: 74432

African (AFR) AF: 0.0441 AC: 1833 AN: 41540

American (AMR) AF: 0.156 AC: 2389 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3472

East Asian (EAS) AF: 0.0828 AC: 429 AN: 5184

South Asian (SAS) AF: 0.186 AC: 899 AN: 4822

European-Finnish (FIN) AF: 0.0980 AC: 1039 AN: 10600

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7050 AN: 68010

Other (OTH) AF: 0.0972 AC: 205 AN: 2110

Alfa AF: 0.104 Hom.: 520

Bravo AF: 0.0934

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		-0.070

Splicing

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

Other links and lift over

dbSNP: rs2332267; hg19: chr1-181426910;