rs2877651

Variant names:

• chr1-181482109-G-A
• rs2877651
• ENST00000524607.6:c.435-1635G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-181482109-G-A
• chr1-181482109-G-C

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.435-1635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 152,300 control chromosomes in the GnomAD database, including 107 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 0.028 (107 hom., cov: 33)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000524607.6	TSL:5	c.435-1635G>A		intron	N/A	ENSP00000432038.2
	ENSG00000297520	ENST00000748511.1		n.484C>T		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000297520	ENST00000748513.1		n.431C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4310 AN: 152182 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0284 AC: 4329 AN: 152300 Hom.: 107 Cov.: 33 AF XY: 0.0284 AC XY: 2114 AN XY: 74474

African (AFR) AF: 0.0241 AC: 1002 AN: 41586

American (AMR) AF: 0.0547 AC: 837 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.131 AC: 674 AN: 5164

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4824

European-Finnish (FIN) AF: 0.00442 AC: 47 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1488 AN: 68008

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0249 Hom.: 66

Bravo AF: 0.0327

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.012
DANN	Benign	0.70
PhyloP100		-2.8

Splicing

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

Other links and lift over

dbSNP: rs2877651; hg19: chr1-181451245;