rs6803199

Variant names:

• chr3-54416166-T-C
• rs6803199
• NM_018398.3:c.381+29392T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018398.3(CACNA2D3):​c.381+29392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,090 control chromosomes in the GnomAD database, including 18,191 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 0.47 (18191 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.916
• Publications: 2 publications found

Genes affected

CACNA2D3 (HGNC:15460): (calcium voltage-gated channel auxiliary subunit alpha2delta 3) 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.381+29392T>C		intron_variant	Intron 4 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.381+29392T>C		intron_variant	Intron 4 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71850 AN: 151972 Hom.: 18193 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.472 AC: 71862 AN: 152090 Hom.: 18191 Cov.: 32 AF XY: 0.474 AC XY: 35220 AN XY: 74336

African (AFR) AF: 0.291 AC: 12072 AN: 41468

American (AMR) AF: 0.432 AC: 6607 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1602 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2139 AN: 5174

South Asian (SAS) AF: 0.554 AC: 2668 AN: 4818

European-Finnish (FIN) AF: 0.597 AC: 6307 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38845 AN: 67990

Other (OTH) AF: 0.500 AC: 1054 AN: 2108

Alfa AF: 0.530 Hom.: 68730

Bravo AF: 0.450

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6803199; hg19: chr3-54450193;