rs10797724

Variant names:

• chr1-181548989-A-G
• rs10797724
• NM_001205293.3:c.513-28777A>G

Variant summary

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

The NM_001205293.3(CACNA1E):​c.513-28777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,120 control chromosomes in the GnomAD database, including 43,234 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 0.73 (43234 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.513-28777A>G		intron	N/A	NP_001192222.1
	CACNA1E	NM_000721.4		c.513-28777A>G		intron	N/A	NP_000712.2
	CACNA1E	NM_001205294.2		c.513-28777A>G		intron	N/A	NP_001192223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.513-28777A>G		intron	N/A	ENSP00000356545.2
	CACNA1E	ENST00000360108.7	TSL:5	c.513-28777A>G		intron	N/A	ENSP00000353222.3
	CACNA1E	ENST00000367570.6	TSL:1	c.513-28777A>G		intron	N/A	ENSP00000356542.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111439 AN: 152002 Hom.: 43225 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.733 AC: 111476 AN: 152120 Hom.: 43234 Cov.: 32 AF XY: 0.733 AC XY: 54521 AN XY: 74358

African (AFR) AF: 0.459 AC: 19035 AN: 41452

American (AMR) AF: 0.752 AC: 11485 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2794 AN: 3468

East Asian (EAS) AF: 0.742 AC: 3841 AN: 5176

South Asian (SAS) AF: 0.718 AC: 3466 AN: 4826

European-Finnish (FIN) AF: 0.861 AC: 9118 AN: 10588

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59060 AN: 68012

Other (OTH) AF: 0.755 AC: 1592 AN: 2110

Alfa AF: 0.829 Hom.: 40205

Bravo AF: 0.713

Asia WGS AF: 0.734 AC: 2556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.66
PhyloP100		0.41
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: rs10797724; hg19: chr1-181518125;