3-54882323-C-G

Variant names:

• chr3-54882323-C-G
• rs1526590
• NM_018398.3:c.1912+1460C>G

Variant summary

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

The NM_018398.3(CACNA2D3):​c.1912+1460C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,176 control chromosomes in the GnomAD database, including 48,696 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 0.79 (48696 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• 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]

CACNA2D3-AS1 (HGNC:40702): (CACNA2D3 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.1912+1460C>G		intron_variant	Intron 21 of 37	ENST00000474759.6	NP_060868.2
CACNA2D3-AS1	NR_046666.1	n.534-3379G>C		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.1912+1460C>G		intron_variant	Intron 21 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120762 AN: 152058 Hom.: 48652 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.794 AC: 120860 AN: 152176 Hom.: 48696 Cov.: 32 AF XY: 0.797 AC XY: 59265 AN XY: 74390

African (AFR) AF: 0.921 AC: 38259 AN: 41532

American (AMR) AF: 0.840 AC: 12842 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2840 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4602 AN: 5180

South Asian (SAS) AF: 0.801 AC: 3868 AN: 4826

European-Finnish (FIN) AF: 0.730 AC: 7727 AN: 10584

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48196 AN: 67974

Other (OTH) AF: 0.782 AC: 1650 AN: 2110

Alfa AF: 0.747 Hom.: 5004

Bravo AF: 0.809

Asia WGS AF: 0.816 AC: 2839 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	0.75
DANN	Benign	0.68
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1526590; hg19: chr3-54916350;