rs1597310

Variant names:

• chr3-54499290-C-T
• rs1597310
• NM_018398.3:c.382-4202C>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.382-4202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 152,166 control chromosomes in the GnomAD database, including 87 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 0.020 (87 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.736
• Publications: 0 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.1 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.382-4202C>T		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.382-4202C>T		intron	N/A	ENSP00000419101.1
	CACNA2D3	ENST00000490478.5	TSL:1	c.100-4202C>T		intron	N/A	ENSP00000417279.1
	CACNA2D3	ENST00000468658.1	TSL:1	n.100-63510C>T		intron	N/A	ENSP00000417455.1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3098 AN: 152048 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0204 AC: 3105 AN: 152166 Hom.: 87 Cov.: 32 AF XY: 0.0236 AC XY: 1757 AN XY: 74388

African (AFR) AF: 0.00339 AC: 141 AN: 41554

American (AMR) AF: 0.0472 AC: 721 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.108 AC: 559 AN: 5182

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4818

European-Finnish (FIN) AF: 0.0450 AC: 477 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 959 AN: 67956

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0156 Hom.: 0

Bravo AF: 0.0192

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		0.74
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: rs1597310; hg19: chr3-54533317;