3-54566416-G-C

Variant names:

• chr3-54566416-G-C
• rs2030395
• NM_018398.3:c.677-3379G>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.677-3379G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,024 control chromosomes in the GnomAD database, including 18,750 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 0.49 (18750 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.57 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	NM_018398.3	MANE Select	c.677-3379G>C		intron	N/A	NP_060868.2	Q8IZS8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.677-3379G>C		intron	N/A	ENSP00000419101.1	Q8IZS8-1
	CACNA2D3	ENST00000490478.5	TSL:1	c.395-3379G>C		intron	N/A	ENSP00000417279.1	Q8IZS8-2
	CACNA2D3	ENST00000468658.1	TSL:1	n.*91-3379G>C		intron	N/A	ENSP00000417455.1	F8WAV4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74600 AN: 151906 Hom.: 18736 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.491 AC: 74654 AN: 152024 Hom.: 18750 Cov.: 32 AF XY: 0.488 AC XY: 36252 AN XY: 74298

African (AFR) AF: 0.408 AC: 16910 AN: 41470

American (AMR) AF: 0.580 AC: 8860 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1681 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1806 AN: 5148

South Asian (SAS) AF: 0.488 AC: 2348 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4876 AN: 10574

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36415 AN: 67958

Other (OTH) AF: 0.533 AC: 1124 AN: 2110

Alfa AF: 0.343 Hom.: 851

Bravo AF: 0.497

Asia WGS AF: 0.430 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.37
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2030395;

hg19: chr3-54600443;