rs681271

Variant names:

• chr1-181514650-G-A
• rs681271
• NM_001205293.3:c.512+3140G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-181514650-G-A
• chr1-181514650-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001205293.3(CACNA1E):​c.512+3140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,692 control chromosomes in the GnomAD database, including 30,884 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 0.61 (30884 hom., cov: 29)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 69

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.512+3140G>A		intron_variant	Intron 3 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.512+3140G>A		intron_variant	Intron 3 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.512+3140G>A		intron_variant	Intron 3 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.512+3140G>A		intron_variant	Intron 3 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.512+3140G>A		intron_variant	Intron 3 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.947+3140G>A		intron_variant	Intron 5 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93052 AN: 151574 Hom.: 30848 Cov.: 29

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.614 AC: 93136 AN: 151692 Hom.: 30884 Cov.: 29 AF XY: 0.612 AC XY: 45345 AN XY: 74112

African (AFR) AF: 0.890 AC: 36836 AN: 41382

American (AMR) AF: 0.528 AC: 8059 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2156 AN: 3462

East Asian (EAS) AF: 0.497 AC: 2542 AN: 5116

South Asian (SAS) AF: 0.588 AC: 2803 AN: 4770

European-Finnish (FIN) AF: 0.490 AC: 5166 AN: 10542

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.496 AC: 33656 AN: 67860

Other (OTH) AF: 0.611 AC: 1289 AN: 2108

Alfa AF: 0.532 Hom.: 84016

Bravo AF: 0.630

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs681271; hg19: chr1-181483786;