rs505738

Variant names:

• chr1-181473340-A-C
• rs505738
• ENST00000524607.6:c.435-10404A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-181473340-A-C
• chr1-181473340-A-G
• chr1-181473340-A-T

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.435-10404A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,054 control chromosomes in the GnomAD database, including 22,881 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 0.54 (22881 hom., cov: 32)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524607.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000524607.6	TSL:5	c.435-10404A>C		intron	N/A	ENSP00000432038.2
	ENSG00000297520	ENST00000748511.1		n.730+8189T>G		intron	N/A
	ENSG00000297520	ENST00000748512.1		n.168+8189T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81585 AN: 151938 Hom.: 22843 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.537 AC: 81674 AN: 152054 Hom.: 22881 Cov.: 32 AF XY: 0.536 AC XY: 39807 AN XY: 74316

African (AFR) AF: 0.692 AC: 28677 AN: 41452

American (AMR) AF: 0.562 AC: 8583 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1335 AN: 5176

South Asian (SAS) AF: 0.493 AC: 2377 AN: 4818

European-Finnish (FIN) AF: 0.454 AC: 4802 AN: 10568

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32613 AN: 67984

Other (OTH) AF: 0.539 AC: 1137 AN: 2108

Alfa AF: 0.476 Hom.: 5599

Bravo AF: 0.549

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.29
PhyloP100		0.038

Splicing

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

Other links and lift over

dbSNP: rs505738; hg19: chr1-181442476;