rs4652663

Positions:

• chr1-181546965-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205293.3(CACNA1E):​c.513-30801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,130 control chromosomes in the GnomAD database, including 2,618 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 0.15 (2618 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.513-30801T>C		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.513-30801T>C		intron_variant		1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.513-30801T>C		intron_variant		5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.513-30801T>C		intron_variant		1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.513-30801T>C		intron_variant		1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.948-30801T>C		intron_variant		5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22987 AN: 152012 Hom.: 2611 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.151 AC: 23026 AN: 152130 Hom.: 2618 Cov.: 32 AF XY: 0.149 AC XY: 11049 AN XY: 74382

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.0799

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0934 Hom.: 1197

Bravo AF: 0.164

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.41

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: rs4652663; hg19: chr1-181516101;