rs4589969

Positions:

• chr3-54262339-C-G
• chr3-54262339-C-T

Variant summary

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

The NM_018398.3(CACNA2D3):​c.205-58103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,852 control chromosomes in the GnomAD database, including 27,978 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 0.60 (27978 hom., cov: 31)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D3	NM_018398.3	c.205-58103C>G		intron_variant		ENST00000474759.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.205-58103C>G		intron_variant		1	NM_018398.3	P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90853 AN: 151734 Hom.: 27986 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.598 AC: 90870 AN: 151852 Hom.: 27978 Cov.: 31 AF XY: 0.592 AC XY: 43966 AN XY: 74208

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.626

Alfa AF: 0.543 Hom.: 1749

Bravo AF: 0.592

Asia WGS AF: 0.579 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.65

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: rs4589969; hg19: chr3-54296366;