1-181483212-CTTTG-C

Variant names:

• chr1-181483212-CTTTG-C
• rs5779103
• ENST00000367570.6:c.-529_-526delGTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000367570.6(CACNA1E):​c.-529_-526delGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,098 control chromosomes in the GnomAD database, including 1,251 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1251 hom., cov: 30)
  • Exomes 𝑓: 0.088 (0 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01
• Publications: 0 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.

• BP6: Variant 1-181483212-CTTTG-C is Benign according to our data. Variant chr1-181483212-CTTTG-C is described in ClinVar as [Benign]. Clinvar id is 1273449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.435-528_435-525delGTTT		intron_variant	Intron 2 of 49		XP_016857732.1
CACNA1E	XM_017002244.2	c.435-528_435-525delGTTT		intron_variant	Intron 2 of 49		XP_016857733.1
CACNA1E	XM_017002251.1	c.435-528_435-525delGTTT		intron_variant	Intron 2 of 49		XP_016857740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367570.6	c.-529_-526delGTTT		5_prime_UTR_variant	Exon 1 of 47	1		ENSP00000356542.1
CACNA1E	ENST00000524607.6	c.435-528_435-525delGTTT		intron_variant	Intron 2 of 11	5		ENSP00000432038.2
CACNA1E	ENST00000533229.1	n.-98_-95delTTTG		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19111 AN: 151912 Hom.: 1249 Cov.: 30

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.0882 AC: 6 AN: 68 Hom.: 0 AF XY: 0.0750 AC XY: 3 AN XY: 40

African (AFR) AF: 0.125 AC: 1 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.100 AC: 1 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0588 AC: 2 AN: 34

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.126 AC: 19111 AN: 152030 Hom.: 1251 Cov.: 30 AF XY: 0.121 AC XY: 8976 AN XY: 74310

African (AFR) AF: 0.122 AC: 5065 AN: 41472

American (AMR) AF: 0.104 AC: 1586 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3472

East Asian (EAS) AF: 0.0632 AC: 326 AN: 5156

South Asian (SAS) AF: 0.0592 AC: 286 AN: 4830

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10556

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9637 AN: 67966

Other (OTH) AF: 0.132 AC: 277 AN: 2104

Alfa AF: 0.138 Hom.: 181

Bravo AF: 0.127

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5779103; hg19: chr1-181452348;