Variant NM_172364.5:c.*1275T>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_172364.5(CACNA2D4):c.*1275T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,262 control chromosomes in the GnomAD database, including 1,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1843 hom., cov: 34)

Exomes 𝑓: 0.091 ( 0 hom. )

Consequence

CACNA2D4
NM_172364.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.02

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:

Genome browser will be placed here

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 12-1792380-A-C is Benign according to our data. Variant chr12-1792380-A-C is described in ClinVar as [Benign]. Clinvar id is 307808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D4	NM_172364.5 link	c.*1275T>G		3_prime_UTR_variant	Exon 38 of 38	ENST00000382722.10	NP_758952.4	Q7Z3S7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA2D4	ENST00000382722 link	c.*1275T>G	3_prime_UTR_variant	Exon 38 of 38	1	NM_172364.5	ENSP00000372169.4	Q7Z3S7-1
CACNA2D4	ENST00000537784.5 link	n.*1882T>G	non_coding_transcript_exon_variant	Exon 15 of 15	1		ENSP00000440231.2	X6RLU5
CACNA2D4	ENST00000537784.5 link	n.*1882T>G	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000440231.2	X6RLU5
CACNA2D4	ENST00000280663.12 link	n.5519T>G	non_coding_transcript_exon_variant	Exon 36 of 36	2

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20982

AN:

152122

Hom.:

1844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0427

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.0857

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.0909

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.125

GnomAD4 genome

AF:

0.138

AC:

20995

AN:

152240

Hom.:

1843

Cov.:

AF XY:

0.137

AC XY:

10181

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0427

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.0857

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.155

Hom.:

410

Bravo

AF:

0.144

Asia WGS

AF:

0.184

AC:

636

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.057

DANN

Benign

0.73

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