1-181744808-T-C

Position:

• chr1-181744808-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.3719+5555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,290 control chromosomes in the GnomAD database, including 54,222 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 0.84 (54222 hom., cov: 34)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.3719+5555T>C		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.3719+5555T>C		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128277 AN: 152172 Hom.: 54165 Cov.: 34

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.843 AC: 128391 AN: 152290 Hom.: 54222 Cov.: 34 AF XY: 0.845 AC XY: 62937 AN XY: 74446

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.825

Alfa AF: 0.852 Hom.: 12307

Bravo AF: 0.835

Asia WGS AF: 0.821 AC: 2858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.60

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: rs3767002; hg19: chr1-181713944;