1-181520031-G-T

Position:

• chr1-181520031-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.512+8521G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,908 control chromosomes in the GnomAD database, including 19,226 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 0.50 (19226 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.512+8521G>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+8521G>T		intron_variant		1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.512+8521G>T		intron_variant		5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.512+8521G>T		intron_variant		1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.512+8521G>T		intron_variant		1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.947+8521G>T		intron_variant		5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75718 AN: 151790 Hom.: 19204 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.499 AC: 75790 AN: 151908 Hom.: 19226 Cov.: 32 AF XY: 0.501 AC XY: 37184 AN XY: 74240

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.501

Alfa AF: 0.423 Hom.: 1990

Bravo AF: 0.497

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.42

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: rs589082; hg19: chr1-181489167;