rs4652673

Variant names:

• chr1-181696033-G-A
• rs4652673
• NM_001205293.3:c.1056-14921G>A

Variant summary

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

The NM_001205293.3(CACNA1E):​c.1056-14921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,916 control chromosomes in the GnomAD database, including 35,741 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 0.68 (35741 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.1056-14921G>A		intron_variant	Intron 7 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.1056-14921G>A		intron_variant	Intron 7 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.1056-14921G>A		intron_variant	Intron 7 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.1056-14921G>A		intron_variant	Intron 7 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.1056-14921G>A		intron_variant	Intron 7 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.1491-14921G>A		intron_variant	Intron 9 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103938 AN: 151798 Hom.: 35713 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.685 AC: 104010 AN: 151916 Hom.: 35741 Cov.: 32 AF XY: 0.688 AC XY: 51075 AN XY: 74262

African (AFR) AF: 0.637 AC: 26360 AN: 41396

American (AMR) AF: 0.627 AC: 9570 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2534 AN: 3470

East Asian (EAS) AF: 0.788 AC: 4079 AN: 5176

South Asian (SAS) AF: 0.655 AC: 3151 AN: 4812

European-Finnish (FIN) AF: 0.717 AC: 7576 AN: 10570

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48428 AN: 67918

Other (OTH) AF: 0.651 AC: 1372 AN: 2108

Alfa AF: 0.698 Hom.: 5615

Bravo AF: 0.674

Asia WGS AF: 0.665 AC: 2315 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	1.7
DANN	Benign	0.71
PhyloP100		0.11
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: rs4652673; hg19: chr1-181665169;