Variant 12-1792998-C-T 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_172364.5(CACNA2D4):c.*657G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,054 control chromosomes in the GnomAD database, including 16,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16538 hom., cov: 32)

Exomes 𝑓: 0.43 ( 7 hom. )

Consequence

CACNA2D4
NM_172364.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.11

Variant links:

Genes affected

CACNA2D4 (HGNC:20202): (calcium voltage-gated channel auxiliary subunit alpha2delta 4) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CACNA2D4 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=-0.88).

BP6

Variant 12-1792998-C-T is Benign according to our data. Variant chr12-1792998-C-T is described in ClinVar as [Benign]. Clinvar id is 307819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D4	NM_172364.5 linkuse as main transcript	c.*657G>A		3_prime_UTR_variant	38/38	ENST00000382722.10	NP_758952.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D4	ENST00000382722.10 linkuse as main transcript	c.*657G>A		3_prime_UTR_variant	38/38	1	NM_172364.5	ENSP00000372169	P2	Q7Z3S7-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65990

AN:

151878

Hom.:

16536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.545

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.431

AC:

AN:

Hom.:

Cov.:

AF XY:

0.344

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.469

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.434

AC:

65996

AN:

151996

Hom.:

16538

Cov.:

AF XY:

0.434

AC XY:

32277

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.482

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.492

Hom.:

8766

Bravo

AF:

0.411

Asia WGS

AF:

0.424

AC:

1479

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinal cone dystrophy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.35

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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