1-181744808-T-C

Variant names:

• chr1-181744808-T-C
• rs3767002
• NM_001205293.3:c.3719+5555T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.58).
• 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 rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.3719+5555T>C		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.3719+5555T>C		intron_variant	Intron 25 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.3662+5555T>C		intron_variant	Intron 24 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.3719+5555T>C		intron_variant	Intron 25 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.3662+5555T>C		intron_variant	Intron 24 of 45	1		ENSP00000481619.1

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

African (AFR) AF: 0.811 AC: 33690 AN: 41534

American (AMR) AF: 0.832 AC: 12727 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2890 AN: 3470

East Asian (EAS) AF: 0.807 AC: 4187 AN: 5186

South Asian (SAS) AF: 0.897 AC: 4329 AN: 4828

European-Finnish (FIN) AF: 0.869 AC: 9228 AN: 10620

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58524 AN: 68036

Other (OTH) AF: 0.825 AC: 1743 AN: 2114

Alfa AF: 0.852 Hom.: 12578

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
PhyloP100		-1.0
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: rs3767002; hg19: chr1-181713944;