3-54713217-C-T

Variant names:

• chr3-54713217-C-T
• rs589281
• NM_018398.3:c.1168-39382C>T

Variant summary

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

The NM_018398.3(CACNA2D3):​c.1168-39382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,078 control chromosomes in the GnomAD database, including 10,585 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 0.36 (10585 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018398.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	NM_018398.3	MANE Select	c.1168-39382C>T		intron	N/A	NP_060868.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.1168-39382C>T		intron	N/A	ENSP00000419101.1
	CACNA2D3	ENST00000490478.5	TSL:1	c.886-39382C>T		intron	N/A	ENSP00000417279.1
	CACNA2D3	ENST00000468658.1	TSL:1	n.*582-39382C>T		intron	N/A	ENSP00000417455.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54031 AN: 151960 Hom.: 10591 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.355 AC: 54035 AN: 152078 Hom.: 10585 Cov.: 32 AF XY: 0.361 AC XY: 26820 AN XY: 74340

African (AFR) AF: 0.174 AC: 7233 AN: 41488

American (AMR) AF: 0.426 AC: 6520 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2541 AN: 5166

South Asian (SAS) AF: 0.413 AC: 1988 AN: 4814

European-Finnish (FIN) AF: 0.462 AC: 4886 AN: 10566

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28196 AN: 67964

Other (OTH) AF: 0.371 AC: 785 AN: 2114

Alfa AF: 0.400 Hom.: 20969

Bravo AF: 0.345

Asia WGS AF: 0.423 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.61
PhyloP100		-0.38
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: rs589281; hg19: chr3-54747244;