rs3767003

Positions:

• chr1-181747522-G-A
• chr1-181747522-G-T

Variant summary

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

The NM_001205293.3(CACNA1E):​c.3720-2954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 150,412 control chromosomes in the GnomAD database, including 23,796 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 0.56 (23796 hom., cov: 28)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.3720-2954G>A		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.3720-2954G>A		intron_variant		1	NM_001205293.3	ENSP00000356545	A2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84251 AN: 150308 Hom.: 23757 Cov.: 28

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.561 AC: 84338 AN: 150412 Hom.: 23796 Cov.: 28 AF XY: 0.564 AC XY: 41369 AN XY: 73342

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.533

Alfa AF: 0.583 Hom.: 44033

Bravo AF: 0.548

Asia WGS AF: 0.620 AC: 2160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.47

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: rs3767003; hg19: chr1-181716658; COSMIC: COSV62386662;