rs6681017

Positions:

• chr1-181539190-C-T

Variant summary

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

The NM_001205293.3(CACNA1E):​c.512+27680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,082 control chromosomes in the GnomAD database, including 4,526 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 0.23 (4526 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.512+27680C>T		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.512+27680C>T		intron_variant		1	NM_001205293.3	ENSP00000356545	A2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35151 AN: 151964 Hom.: 4514 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.231 AC: 35196 AN: 152082 Hom.: 4526 Cov.: 32 AF XY: 0.225 AC XY: 16724 AN XY: 74362

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0782

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.198

Alfa AF: 0.210 Hom.: 3344

Bravo AF: 0.241

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.43

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: rs6681017; hg19: chr1-181508326;