1-181520031-G-T

Variant names:

• chr1-181520031-G-T
• rs589082
• NM_001205293.3:c.512+8521G>T

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+8521G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,908 control chromosomes in the GnomAD database, including 19,226 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 0.50 (19226 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205293.3. 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
	CACNA1E	NM_001205293.3	MANE Select	c.512+8521G>T		intron	N/A	NP_001192222.1	Q15878-1
	CACNA1E	NM_000721.4		c.512+8521G>T		intron	N/A	NP_000712.2	Q15878-3
	CACNA1E	NM_001205294.2		c.512+8521G>T		intron	N/A	NP_001192223.1	Q15878-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.512+8521G>T		intron	N/A	ENSP00000356545.2	Q15878-1
	CACNA1E	ENST00000360108.7	TSL:5	c.512+8521G>T		intron	N/A	ENSP00000353222.3	F8W9Z1
	CACNA1E	ENST00000367570.6	TSL:1	c.512+8521G>T		intron	N/A	ENSP00000356542.1	Q15878-3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75718 AN: 151790 Hom.: 19204 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.499 AC: 75790 AN: 151908 Hom.: 19226 Cov.: 32 AF XY: 0.501 AC XY: 37184 AN XY: 74240

African (AFR) AF: 0.439 AC: 18196 AN: 41416

American (AMR) AF: 0.548 AC: 8359 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1733 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2587 AN: 5172

South Asian (SAS) AF: 0.569 AC: 2738 AN: 4814

European-Finnish (FIN) AF: 0.506 AC: 5319 AN: 10508

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35228 AN: 67960

Other (OTH) AF: 0.501 AC: 1055 AN: 2106

Alfa AF: 0.423 Hom.: 2064

Bravo AF: 0.497

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.42
PhyloP100		-1.9
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: rs589082; hg19: chr1-181489167;