rs7513685

Positions:

• chr1-181807783-G-A

Variant summary

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

The NM_001205293.3(CACNA1E):​c.*8949G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,026 control chromosomes in the GnomAD database, including 69 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 0.028 (69 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CACNA1E NM_001205293.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.*8949G>A		3_prime_UTR_variant	48/48	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.*8949G>A		3_prime_UTR_variant	48/48	1	NM_001205293.3	ENSP00000356545	A2
CACNA1E	ENST00000621791.4	c.*8949G>A		3_prime_UTR_variant	46/46	1		ENSP00000481619	A2
CACNA1E	ENST00000700190.1	c.499-4535G>A		intron_variant				ENSP00000514852

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4256 AN: 151908 Hom.: 68 Cov.: 31

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0230

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0280 AC: 4256 AN: 152026 Hom.: 69 Cov.: 31 AF XY: 0.0297 AC XY: 2207 AN XY: 74282

Gnomad4 AFR AF: 0.0329

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0224 Hom.: 33

Bravo AF: 0.0272

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7513685; hg19: chr1-181776918;