rs7540850

Variant names:

• chr1-181717080-T-C
• rs7540850
• NM_001205293.3:c.1316-13T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-181717080-T-C
• chr1-181717080-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000367573.7(CACNA1E):​c.1316-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,610,998 control chromosomes in the GnomAD database, including 406,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (30270 hom., cov: 33)
  • Exomes 𝑓: 0.71 (376464 hom.)
• Consequence: CACNA1E ENST00000367573.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.190
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-181717080-T-C is Benign according to our data. Variant chr1-181717080-T-C is described in ClinVar as Benign. ClinVar VariationId is 1192683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367573.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.1316-13T>C		intron	N/A	NP_001192222.1
	CACNA1E	NM_000721.4		c.1316-13T>C		intron	N/A	NP_000712.2
	CACNA1E	NM_001205294.2		c.1316-13T>C		intron	N/A	NP_001192223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.1316-13T>C		intron	N/A	ENSP00000356545.2
	CACNA1E	ENST00000360108.7	TSL:5	c.1316-13T>C		intron	N/A	ENSP00000353222.3
	CACNA1E	ENST00000367570.6	TSL:1	c.1316-13T>C		intron	N/A	ENSP00000356542.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91163 AN: 152078 Hom.: 30249 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.599

GnomAD2 exomes AF: 0.681 AC: 169553 AN: 248938 AF XY: 0.688

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.645

Gnomad ASJ exome AF: 0.708

Gnomad EAS exome AF: 0.754

Gnomad FIN exome AF: 0.757

Gnomad NFE exome AF: 0.726

Gnomad OTH exome AF: 0.699

GnomAD4 exome AF: 0.714 AC: 1041334 AN: 1458802 Hom.: 376464 Cov.: 33 AF XY: 0.713 AC XY: 517811 AN XY: 725946

African (AFR) AF: 0.272 AC: 9076 AN: 33414

American (AMR) AF: 0.651 AC: 29128 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 18563 AN: 26106

East Asian (EAS) AF: 0.788 AC: 31256 AN: 39686

South Asian (SAS) AF: 0.652 AC: 56231 AN: 86204

European-Finnish (FIN) AF: 0.756 AC: 40358 AN: 53384

Middle Eastern (MID) AF: 0.614 AC: 3535 AN: 5754

European-Non Finnish (NFE) AF: 0.731 AC: 811324 AN: 1109278

Other (OTH) AF: 0.695 AC: 41863 AN: 60262

GnomAD4 genome AF: 0.599 AC: 91215 AN: 152196 Hom.: 30270 Cov.: 33 AF XY: 0.605 AC XY: 45020 AN XY: 74424

African (AFR) AF: 0.286 AC: 11897 AN: 41526

American (AMR) AF: 0.661 AC: 10105 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2468 AN: 3468

East Asian (EAS) AF: 0.768 AC: 3972 AN: 5174

South Asian (SAS) AF: 0.655 AC: 3159 AN: 4826

European-Finnish (FIN) AF: 0.760 AC: 8055 AN: 10594

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49465 AN: 68006

Other (OTH) AF: 0.603 AC: 1270 AN: 2106

Alfa AF: 0.673 Hom.: 47976

Bravo AF: 0.577

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Developmental and epileptic encephalopathy, 69 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.29
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7540850; hg19: chr1-181686216; COSMIC: COSV62386641; COSMIC: COSV62386641;