3-54983722-A-G

Variant names:

• chr3-54983722-A-G
• rs3773582
• NM_018398.3:c.2557-886A>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.2557-886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,208 control chromosomes in the GnomAD database, including 2,705 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 0.18 (2705 hom., cov: 33)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 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.2557-886A>G		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.2557-886A>G		intron	N/A	ENSP00000419101.1
	CACNA2D3	ENST00000490478.5	TSL:1	c.2275-886A>G		intron	N/A	ENSP00000417279.1
	CACNA2D3	ENST00000471363.5	TSL:1	n.*635-886A>G		intron	N/A	ENSP00000418228.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26906 AN: 152090 Hom.: 2706 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.177 AC: 26926 AN: 152208 Hom.: 2705 Cov.: 33 AF XY: 0.183 AC XY: 13595 AN XY: 74424

African (AFR) AF: 0.101 AC: 4214 AN: 41548

American (AMR) AF: 0.285 AC: 4366 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1620 AN: 5178

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4826

European-Finnish (FIN) AF: 0.211 AC: 2230 AN: 10592

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12048 AN: 67990

Other (OTH) AF: 0.185 AC: 390 AN: 2108

Alfa AF: 0.183 Hom.: 10519

Bravo AF: 0.180

Asia WGS AF: 0.284 AC: 985 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		1.7
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: rs3773582; hg19: chr3-55017749;