rs17494681

chr1-181511047-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.373-324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,244 control chromosomes in the GnomAD database, including 1,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1729 hom., cov: 33)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441

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=-0.89).
• BP6: Variant 1-181511047-C-T is Benign according to our data. Variant chr1-181511047-C-T is described in ClinVar as [Benign]. Clinvar id is 1296142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.373-324C>T		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.373-324C>T		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21629 AN: 152126 Hom.: 1730 Cov.: 33

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.142 AC: 21624 AN: 152244 Hom.: 1729 Cov.: 33 AF XY: 0.142 AC XY: 10534 AN XY: 74428

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0697

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.167

Alfa AF: 0.174 Hom.: 3000

Bravo AF: 0.139

Asia WGS AF: 0.0970 AC: 338 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 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.59
Dann	Benign	0.71

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: rs17494681; hg19: chr1-181480183;