Genetic Variant CACNA1E:c.-237_-236insCT (chr1-181483507-T-TTC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000367570.6(CACNA1E):c.-237_-236insCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 344,410 control chromosomes in the GnomAD database, including 349 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 291 hom., cov: 30)

Exomes 𝑓: 0.0037 ( 58 hom. )

Consequence

CACNA1E
ENST00000367570.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0920

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-181483507-T-TTC is Benign according to our data. Variant chr1-181483507-T-TTC is described in ClinVar as [Benign]. Clinvar id is 1238863.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3 link	c.-238_-237insTC		upstream_gene_variant		ENST00000367573.7	NP_001192222.1	Q15878-1Q59FG1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1E	ENST00000367570.6 link	c.-237_-236insCT	5_prime_UTR_variant	Exon 1 of 47	1		ENSP00000356542.1	Q15878-3
CACNA1E	ENST00000524607.6 link	c.435-236_435-235insCT	intron_variant	Intron 2 of 11	5		ENSP00000432038.2	E9PIE8
CACNA1E	ENST00000367573.7 link	c.-238_-237insTC	upstream_gene_variant		1	NM_001205293.3	ENSP00000356545.2	Q15878-1
CACNA1E	ENST00000360108.7 link	c.-238_-237insTC	upstream_gene_variant		5		ENSP00000353222.3	F8W9Z1
CACNA1E	ENST00000621791.4 link	c.-238_-237insTC	upstream_gene_variant		1		ENSP00000481619.1	Q15878-2

Frequencies

GnomAD3 genomes

AF:

0.0328

AC:

4958

AN:

151264

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000546

Gnomad OTH

AF:

0.0251

GnomAD4 exome

AF:

0.00373

AC:

720

AN:

193030

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

320

AN XY:

98262

show subpopulations

African (AFR)

AF:

0.0958

AC:

496

AN:

5178

American (AMR)

AF:

0.00872

AC:

AN:

5732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7354

East Asian (EAS)

AF:

0.00

AC:

AN:

17306

South Asian (SAS)

AF:

0.00

AC:

AN:

2534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15898

Middle Eastern (MID)

AF:

0.00377

AC:

AN:

1060

European-Non Finnish (NFE)

AF:

0.000344

AC:

AN:

124990

Other (OTH)

AF:

0.00979

AC:

127

AN:

12978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.609

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0329

AC:

4973

AN:

151380

Hom.:

291

Cov.:

AF XY:

0.0322

AC XY:

2382

AN XY:

73994

show subpopulations

African (AFR)

AF:

0.112

AC:

4613

AN:

41146

American (AMR)

AF:

0.0175

AC:

266

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.000208

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10458

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000546

AC:

AN:

67814

Other (OTH)

AF:

0.0248

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

208

417

625

834

1042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 28, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.092

Splicing

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

Publications

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1-181483507-T-TTC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over