rs3767004

Variant names:

• chr1-181747911-G-A
• rs3767004
• NM_001205293.3:c.3720-2565G>A

Variant summary

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

The NM_001205293.3(CACNA1E):​c.3720-2565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,146 control chromosomes in the GnomAD database, including 994 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 0.10 (994 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.3720-2565G>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.3720-2565G>A		intron_variant	Intron 25 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.3663-2565G>A		intron_variant	Intron 24 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.3720-2565G>A		intron_variant	Intron 25 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.3663-2565G>A		intron_variant	Intron 24 of 45	1		ENSP00000481619.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15515 AN: 152028 Hom.: 986 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.102 AC: 15555 AN: 152146 Hom.: 994 Cov.: 32 AF XY: 0.103 AC XY: 7678 AN XY: 74356

African (AFR) AF: 0.136 AC: 5659 AN: 41488

American (AMR) AF: 0.114 AC: 1745 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1575 AN: 5174

South Asian (SAS) AF: 0.0660 AC: 318 AN: 4816

European-Finnish (FIN) AF: 0.0637 AC: 675 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0737 AC: 5011 AN: 68010

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.0813 Hom.: 923

Bravo AF: 0.110

Asia WGS AF: 0.163 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		0.14
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: rs3767004; hg19: chr1-181717047;