NM_018398.3:c.2988-10544G>A

Variant names:

• chr3-55062901-G-A
• rs3773540
• NM_018398.3:c.2988-10544G>A

Variant summary

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

The NM_018398.3(CACNA2D3):​c.2988-10544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,132 control chromosomes in the GnomAD database, including 3,651 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 0.16 (3651 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 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.2988-10544G>A		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.2988-10544G>A		intron	N/A	ENSP00000419101.1
	CACNA2D3	ENST00000490478.5	TSL:1	c.2706-10544G>A		intron	N/A	ENSP00000417279.1
	CACNA2D3	ENST00000471363.5	TSL:1	n.*1066-10544G>A		intron	N/A	ENSP00000418228.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24216 AN: 152014 Hom.: 3628 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.160 AC: 24288 AN: 152132 Hom.: 3651 Cov.: 32 AF XY: 0.166 AC XY: 12312 AN XY: 74390

African (AFR) AF: 0.345 AC: 14288 AN: 41474

American (AMR) AF: 0.292 AC: 4453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0672 AC: 233 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1453 AN: 5164

South Asian (SAS) AF: 0.153 AC: 737 AN: 4824

European-Finnish (FIN) AF: 0.0733 AC: 777 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1991 AN: 68010

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.0680 Hom.: 1901

Bravo AF: 0.189

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.015
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: rs3773540; hg19: chr3-55096928;