rs473200

Variant names:

• chr1-181785667-C-A
• rs473200
• NM_001205293.3:c.5680-46C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-181785667-C-A
• chr1-181785667-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001205293.3(CACNA1E):​c.5680-46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,282,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (1 hom.)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.444
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-181785667-C-A is Benign according to our data. Variant chr1-181785667-C-A is described in ClinVar as Benign. ClinVar VariationId is 1231223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205293.3. 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.5680-46C>A		intron	N/A	NP_001192222.1
	CACNA1E	NM_000721.4		c.5680-46C>A		intron	N/A	NP_000712.2
	CACNA1E	NM_001205294.2		c.5623-46C>A		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.5680-46C>A		intron	N/A	ENSP00000356545.2
	CACNA1E	ENST00000360108.7	TSL:5	c.5623-46C>A		intron	N/A	ENSP00000353222.3
	CACNA1E	ENST00000367570.6	TSL:1	c.5680-46C>A		intron	N/A	ENSP00000356542.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000167 AC: 41 AN: 245516 AF XY: 0.000187

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000787 AC: 89 AN: 1130704 Hom.: 1 Cov.: 15 AF XY: 0.000116 AC XY: 67 AN XY: 578504

African (AFR) AF: 0.00 AC: 0 AN: 26818

American (AMR) AF: 0.00 AC: 0 AN: 43308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24126

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38132

South Asian (SAS) AF: 0.00108 AC: 85 AN: 78900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5170

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 811472

Other (OTH) AF: 0.0000404 AC: 2 AN: 49546

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74414

African (AFR) AF: 0.00 AC: 0 AN: 41494

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 11998

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.62
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism

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: rs473200; hg19: chr1-181754803;