chr3-54869588-A-C

Variant names:

• chr3-54869588-A-C
• rs2703029
• NM_018398.3:c.1627-1951A>C

Variant summary

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

The NM_018398.3(CACNA2D3):​c.1627-1951A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,036 control chromosomes in the GnomAD database, including 31,388 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 0.64 (31388 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.1627-1951A>C		intron_variant	Intron 17 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.1627-1951A>C		intron_variant	Intron 17 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96523 AN: 151918 Hom.: 31354 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.635 AC: 96607 AN: 152036 Hom.: 31388 Cov.: 32 AF XY: 0.646 AC XY: 47990 AN XY: 74316

African (AFR) AF: 0.718 AC: 29773 AN: 41452

American (AMR) AF: 0.735 AC: 11234 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3470

East Asian (EAS) AF: 0.874 AC: 4508 AN: 5158

South Asian (SAS) AF: 0.666 AC: 3210 AN: 4818

European-Finnish (FIN) AF: 0.631 AC: 6681 AN: 10584

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36982 AN: 67946

Other (OTH) AF: 0.628 AC: 1325 AN: 2110

Alfa AF: 0.575 Hom.: 81573

Bravo AF: 0.650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	10
DANN	Benign	0.54
PhyloP100		0.48
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: rs2703029; hg19: chr3-54903615;