12-1885952-C-T

Position:

chr12-1885952-C-T

Variant summary

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

The NM_172364.5(CACNA2D4):c.1068+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,600,026 control chromosomes in the GnomAD database, including 9,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1401 hom., cov: 31)

Exomes 𝑓: 0.10 ( 8255 hom. )

Consequence

CACNA2D4
NM_172364.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.29

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:

LOC124902858 (HGNC:):

LOC124902858 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=-0.9).

BP6

Variant 12-1885952-C-T is Benign according to our data. Variant chr12-1885952-C-T is described in ClinVar as [Benign]. Clinvar id is 262808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D4	NM_172364.5 linkuse as main transcript	c.1068+13G>A		intron_variant		ENST00000382722.10
LOC124902858	XR_007063158.1 linkuse as main transcript	n.196C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D4	ENST00000382722.10 linkuse as main transcript	c.1068+13G>A		intron_variant		1	NM_172364.5	P2	Q7Z3S7-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18606

AN:

151844

Hom.:

1392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0305

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0826

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0996

AC:

24360

AN:

244538

Hom.:

1394

AF XY:

0.102

AC XY:

13525

AN XY:

132472

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.0336

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0909

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0997

GnomAD4 exome

AF:

0.103

AC:

148529

AN:

1448064

Hom.:

8255

Cov.:

AF XY:

0.104

AC XY:

74660

AN XY:

720716

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0420

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.0908

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.123

AC:

18652

AN:

151962

Hom.:

1401

Cov.:

AF XY:

0.120

AC XY:

8880

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.0732

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.0826

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.115

Hom.:

209

Bravo

AF:

0.121

Asia WGS

AF:

0.119

AC:

412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.33

DANN

Benign

0.88

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