1-181809194-C-A

Variant names:

• chr1-181809194-C-A
• rs610100
• ENST00000661326.1:n.1772G>T

Variant summary

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

The ENST00000661326.1(ENSG00000287452):​n.1772G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,062 control chromosomes in the GnomAD database, including 25,690 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 0.57 (25690 hom., cov: 32)
• Consequence: ENSG00000287452 ENST00000661326.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 1 publications found

Genes affected

ENSG00000287452 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287452	ENST00000661326.1	n.1772G>T		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000287452	ENST00000717053.1	n.652G>T		non_coding_transcript_exon_variant	Exon 4 of 4
ENSG00000287452	ENST00000717054.1	n.677G>T		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87022 AN: 151944 Hom.: 25661 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.573 AC: 87096 AN: 152062 Hom.: 25690 Cov.: 32 AF XY: 0.568 AC XY: 42212 AN XY: 74336

African (AFR) AF: 0.452 AC: 18746 AN: 41466

American (AMR) AF: 0.506 AC: 7725 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2037 AN: 5160

South Asian (SAS) AF: 0.562 AC: 2707 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6519 AN: 10586

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45097 AN: 67974

Other (OTH) AF: 0.597 AC: 1261 AN: 2112

Alfa AF: 0.630 Hom.: 71519

Bravo AF: 0.557

Asia WGS AF: 0.473 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.71
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs610100; hg19: chr1-181778329;