rs601059

chr1-181790116-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.5787-329C>T		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.5787-329C>T		intron_variant		1	NM_001205293.3	A2
CACNA1E	ENST00000367570.6	c.5787-329C>T		intron_variant		1		P4
CACNA1E	ENST00000621791.4	c.5730-329C>T		intron_variant		1		A2
CACNA1E	ENST00000360108.7	c.5730-329C>T		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.225

Alfa AF: 0.197 Hom.: 472

Bravo AF: 0.207

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.070
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs601059; hg19: chr1-181759252;