rs616113

Variant names:

• chr3-54630621-G-A
• rs616113
• NM_018398.3:c.1053+2745G>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.1053+2745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,980 control chromosomes in the GnomAD database, including 16,676 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 0.46 (16676 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.1053+2745G>A		intron_variant	Intron 10 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.1053+2745G>A		intron_variant	Intron 10 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69643 AN: 151862 Hom.: 16679 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.458 AC: 69643 AN: 151980 Hom.: 16676 Cov.: 32 AF XY: 0.458 AC XY: 33980 AN XY: 74270

African (AFR) AF: 0.307 AC: 12737 AN: 41454

American (AMR) AF: 0.515 AC: 7856 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1930 AN: 3468

East Asian (EAS) AF: 0.500 AC: 2575 AN: 5148

South Asian (SAS) AF: 0.439 AC: 2116 AN: 4822

European-Finnish (FIN) AF: 0.494 AC: 5204 AN: 10542

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.523 AC: 35572 AN: 67962

Other (OTH) AF: 0.495 AC: 1046 AN: 2112

Alfa AF: 0.478 Hom.: 2286

Bravo AF: 0.454

Asia WGS AF: 0.459 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.54
PhyloP100		0.15
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: rs616113; hg19: chr3-54664648;