chr1-181483501-C-CTTT

Position:

• chr1-181483501-C-CTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000367570.6(CACNA1E):​c.-232_-230dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 210,814 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (15 hom., cov: 29)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-181483501-C-CTTT is Benign according to our data. Variant chr1-181483501-C-CTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1301079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00798 (1111/139218) while in subpopulation AFR AF= 0.0286 (1069/37418). AF 95% confidence interval is 0.0271. There are 15 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3			upstream_gene_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367570.6	c.-232_-230dup		5_prime_UTR_variant	1/47	1		P4
CACNA1E	ENST00000533229.1	n.203_205dup		non_coding_transcript_exon_variant	1/7	1
CACNA1E	ENST00000524607.6	c.435-231_435-229dup		intron_variant		5
CACNA1E	ENST00000367573.7			upstream_gene_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.00797 AC: 1110 AN: 139186 Hom.: 15 Cov.: 29

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00202

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000241

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000931

Gnomad OTH AF: 0.00369

GnomAD4 exome AF: 0.000265 AC: 19 AN: 71596 Hom.: 0 Cov.: 0 AF XY: 0.000242 AC XY: 9 AN XY: 37238

Gnomad4 AFR exome AF: 0.00533

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000143

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000640

Gnomad4 OTH exome AF: 0.000846

GnomAD4 genome AF: 0.00798 AC: 1111 AN: 139218 Hom.: 15 Cov.: 29 AF XY: 0.00732 AC XY: 494 AN XY: 67458

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.00201

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000242

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000931

Gnomad4 OTH AF: 0.00367

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111237511; hg19: chr1-181452637;