1-181466918-T-C

Variant names:

• chr1-181466918-T-C
• rs644796
• ENST00000524607.6:c.435-16826T>C

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.435-16826T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,122 control chromosomes in the GnomAD database, including 24,582 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 0.55 (24582 hom., cov: 32)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• 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 = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.435-16826T>C		intron_variant	Intron 2 of 49		XP_016857732.1
CACNA1E	XM_017002244.2	c.435-16826T>C		intron_variant	Intron 2 of 49		XP_016857733.1
CACNA1E	XM_017002251.1	c.435-16826T>C		intron_variant	Intron 2 of 49		XP_016857740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000524607.6	c.435-16826T>C		intron_variant	Intron 2 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84065 AN: 152004 Hom.: 24535 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.553 AC: 84164 AN: 152122 Hom.: 24582 Cov.: 32 AF XY: 0.550 AC XY: 40927 AN XY: 74390

African (AFR) AF: 0.746 AC: 30957 AN: 41514

American (AMR) AF: 0.571 AC: 8724 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1568 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5174

South Asian (SAS) AF: 0.493 AC: 2370 AN: 4808

European-Finnish (FIN) AF: 0.454 AC: 4809 AN: 10582

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.481 AC: 32684 AN: 67982

Other (OTH) AF: 0.557 AC: 1178 AN: 2116

Alfa AF: 0.499 Hom.: 10153

Bravo AF: 0.568

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.35
PhyloP100		0.070

Splicing

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

Other links and lift over

dbSNP: rs644796; hg19: chr1-181436054;