rs2013064

chr12-1888878-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172364.5(CACNA2D4):c.782-1809G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,274 control chromosomes in the GnomAD database, including 63,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (63946 hom., cov: 32)
• Consequence: CACNA2D4 NM_172364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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]

LOC124902858 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D4	NM_172364.5	c.782-1809G>A		intron_variant		ENST00000382722.10
LOC124902858	XR_007063158.1	n.2917C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D4	ENST00000382722.10	c.782-1809G>A		intron_variant		1	NM_172364.5	P2

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139241 AN: 152156 Hom.: 63882 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.890

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.915 AC: 139364 AN: 152274 Hom.: 63946 Cov.: 32 AF XY: 0.915 AC XY: 68147 AN XY: 74454

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.891

Alfa AF: 0.892 Hom.: 27865

Bravo AF: 0.918

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.19
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs2013064; hg19: chr12-1998044;