rs1997463

Variant names:

• chr3-54773213-A-G
• rs1997463
• NM_018398.3:c.1380+8862A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-54773213-A-G
• chr3-54773213-A-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.1380+8862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,132 control chromosomes in the GnomAD database, including 10,529 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 0.35 (10529 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 4 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.1380+8862A>G		intron_variant	Intron 13 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.1380+8862A>G		intron_variant	Intron 13 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52496 AN: 152014 Hom.: 10503 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.346 AC: 52568 AN: 152132 Hom.: 10529 Cov.: 32 AF XY: 0.346 AC XY: 25733 AN XY: 74354

African (AFR) AF: 0.559 AC: 23176 AN: 41466

American (AMR) AF: 0.221 AC: 3380 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2079 AN: 5182

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3535 AN: 10572

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17286 AN: 68006

Other (OTH) AF: 0.309 AC: 654 AN: 2114

Alfa AF: 0.264 Hom.: 11575

Bravo AF: 0.349

Asia WGS AF: 0.332 AC: 1160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		1.5
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: rs1997463; hg19: chr3-54807240;