Variant 1-181771607-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001205293.3(CACNA1E):c.4973+223A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 530,108 control chromosomes in the GnomAD database, including 17,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5155 hom., cov: 32)

Exomes 𝑓: 0.24 ( 11977 hom. )

Consequence

CACNA1E
NM_001205293.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.756

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:

RNA5SP70 (HGNC:42847): (RNA, 5S ribosomal pseudogene 70)

RNA5SP70 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-181771607-A-G is Benign according to our data. Variant chr1-181771607-A-G is described in ClinVar as [Benign]. Clinvar id is 1259869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3 linkuse as main transcript	c.4973+223A>G		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7 linkuse as main transcript	c.4973+223A>G		intron_variant		1	NM_001205293.3	ENSP00000356545	A2	Q15878-1
RNA5SP70	ENST00000517168.1 linkuse as main transcript	n.42A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39110

AN:

152022

Hom.:

5150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.0653

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.276

GnomAD4 exome

AF:

0.241

AC:

91253

AN:

377968

Hom.:

11977

Cov.:

AF XY:

0.245

AC XY:

47877

AN XY:

195298

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.0606

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.242

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.257

AC:

39138

AN:

152140

Hom.:

5155

Cov.:

AF XY:

0.257

AC XY:

19087

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.0645

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.258

Hom.:

625

Bravo

AF:

0.259

Asia WGS

AF:

0.193

AC:

668

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.77

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over