1-181734140-T-G

Variant names:

• chr1-181734140-T-G
• rs12139677
• NM_001205293.3:c.3262+390T>G

Variant summary

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

The NM_001205293.3(CACNA1E):​c.3262+390T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,908 control chromosomes in the GnomAD database, including 28,717 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 (28717 hom., cov: 31)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.3262+390T>G		intron_variant	Intron 21 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.3262+390T>G		intron_variant	Intron 21 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.3205+390T>G		intron_variant	Intron 20 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.3262+390T>G		intron_variant	Intron 21 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.3205+390T>G		intron_variant	Intron 20 of 45	1		ENSP00000481619.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92514 AN: 151790 Hom.: 28696 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.609 AC: 92575 AN: 151908 Hom.: 28717 Cov.: 31 AF XY: 0.608 AC XY: 45133 AN XY: 74246

African (AFR) AF: 0.624 AC: 25798 AN: 41352

American (AMR) AF: 0.507 AC: 7754 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2394 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1599 AN: 5156

South Asian (SAS) AF: 0.550 AC: 2649 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6876 AN: 10558

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43445 AN: 67944

Other (OTH) AF: 0.586 AC: 1236 AN: 2110

Alfa AF: 0.617 Hom.: 15472

Bravo AF: 0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.84
PhyloP100		-0.33
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: rs12139677; hg19: chr1-181703276;