chr1-181790116-C-T

Variant names:

• chr1-181790116-C-T
• rs601059
• NM_001205293.3:c.5787-329C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001205293.3(CACNA1E):​c.5787-329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,964 control chromosomes in the GnomAD database, including 3,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3368 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15
• 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-181790116-C-T is Benign according to our data. Variant chr1-181790116-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.5787-329C>T		intron	N/A	NP_001192222.1
	CACNA1E	NM_000721.4		c.5787-329C>T		intron	N/A	NP_000712.2
	CACNA1E	NM_001205294.2		c.5730-329C>T		intron	N/A	NP_001192223.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.5787-329C>T		intron	N/A	ENSP00000356545.2
	CACNA1E	ENST00000360108.7	TSL:5	c.5730-329C>T		intron	N/A	ENSP00000353222.3
	CACNA1E	ENST00000367570.6	TSL:1	c.5787-329C>T		intron	N/A	ENSP00000356542.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31701 AN: 151846 Hom.: 3365 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.209 AC: 31706 AN: 151964 Hom.: 3368 Cov.: 32 AF XY: 0.211 AC XY: 15701 AN XY: 74238

African (AFR) AF: 0.232 AC: 9593 AN: 41420

American (AMR) AF: 0.181 AC: 2772 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1285 AN: 5146

South Asian (SAS) AF: 0.302 AC: 1458 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2126 AN: 10538

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13018 AN: 67982

Other (OTH) AF: 0.225 AC: 473 AN: 2106

Alfa AF: 0.197 Hom.: 472

Bravo AF: 0.207

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.070
DANN	Benign	0.49
PhyloP100		-1.1
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: rs601059; hg19: chr1-181759252;