rs3767003

Variant names:

• chr1-181747522-G-A
• rs3767003
• NM_001205293.3:c.3720-2954G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-181747522-G-A
• chr1-181747522-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205293.3(CACNA1E):​c.3720-2954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 150,412 control chromosomes in the GnomAD database, including 23,796 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 0.56 (23796 hom., cov: 28)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.3720-2954G>A		intron_variant	Intron 25 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.3720-2954G>A		intron_variant	Intron 25 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.3663-2954G>A		intron_variant	Intron 24 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.3720-2954G>A		intron_variant	Intron 25 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.3663-2954G>A		intron_variant	Intron 24 of 45	1		ENSP00000481619.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84251 AN: 150308 Hom.: 23757 Cov.: 28

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.561 AC: 84338 AN: 150412 Hom.: 23796 Cov.: 28 AF XY: 0.564 AC XY: 41369 AN XY: 73342

African (AFR) AF: 0.482 AC: 19648 AN: 40770

American (AMR) AF: 0.531 AC: 8039 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2106 AN: 3460

East Asian (EAS) AF: 0.744 AC: 3812 AN: 5122

South Asian (SAS) AF: 0.543 AC: 2572 AN: 4736

European-Finnish (FIN) AF: 0.615 AC: 6218 AN: 10118

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40117 AN: 67786

Other (OTH) AF: 0.533 AC: 1110 AN: 2084

Alfa AF: 0.579 Hom.: 104571

Bravo AF: 0.548

Asia WGS AF: 0.620 AC: 2160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.47
PhyloP100		-0.037
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: rs3767003; hg19: chr1-181716658; COSMIC: COSV62386662;