1-181683975-T-C

Variant names:

• chr1-181683975-T-C
• rs10910979
• NM_001205293.3:c.1056-26979T>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.1056-26979T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,038 control chromosomes in the GnomAD database, including 18,645 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 0.46 (18645 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 5 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=-0.91).
• 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.1056-26979T>C		intron_variant	Intron 7 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.1056-26979T>C		intron_variant	Intron 7 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.1056-26979T>C		intron_variant	Intron 7 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.1056-26979T>C		intron_variant	Intron 7 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.1056-26979T>C		intron_variant	Intron 7 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.1491-26979T>C		intron_variant	Intron 9 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70524 AN: 151920 Hom.: 18634 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.464 AC: 70550 AN: 152038 Hom.: 18645 Cov.: 32 AF XY: 0.469 AC XY: 34826 AN XY: 74296

African (AFR) AF: 0.203 AC: 8426 AN: 41504

American (AMR) AF: 0.475 AC: 7262 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3858 AN: 5180

South Asian (SAS) AF: 0.407 AC: 1961 AN: 4816

European-Finnish (FIN) AF: 0.605 AC: 6377 AN: 10532

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38948 AN: 67930

Other (OTH) AF: 0.451 AC: 952 AN: 2112

Alfa AF: 0.537 Hom.: 87134

Bravo AF: 0.444

Asia WGS AF: 0.523 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		0.31
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: rs10910979; hg19: chr1-181653111;