rs3856087

Variant names:

• chr1-181455397-G-A
• rs3856087
• ENST00000524607.6:c.435-28347G>A

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.435-28347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,996 control chromosomes in the GnomAD database, including 15,866 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 0.43 (15866 hom., cov: 31)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• 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

ENSG00000297520 (HGNC:):

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 = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.435-28347G>A		intron_variant	Intron 2 of 49		XP_016857732.1
CACNA1E	XM_017002244.2	c.435-28347G>A		intron_variant	Intron 2 of 49		XP_016857733.1
CACNA1E	XM_017002251.1	c.435-28347G>A		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.435-28347G>A		intron_variant	Intron 2 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65591 AN: 151878 Hom.: 15828 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.432 AC: 65676 AN: 151996 Hom.: 15866 Cov.: 31 AF XY: 0.424 AC XY: 31507 AN XY: 74288

African (AFR) AF: 0.667 AC: 27619 AN: 41422

American (AMR) AF: 0.387 AC: 5903 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3470

East Asian (EAS) AF: 0.160 AC: 826 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4818

European-Finnish (FIN) AF: 0.315 AC: 3326 AN: 10554

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24027 AN: 67972

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.370 Hom.: 8229

Bravo AF: 0.448

Asia WGS AF: 0.276 AC: 962 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	0.086
DANN	Benign	0.71
PhyloP100		-2.9

Splicing

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

Other links and lift over

dbSNP: rs3856087; hg19: chr1-181424533;