3-55001847-C-T

Variant names:

• chr3-55001847-C-T
• rs4955826
• NM_018398.3:c.2691-2916C>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.2691-2916C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,034 control chromosomes in the GnomAD database, including 12,449 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 0.39 (12449 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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 (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.2691-2916C>T		intron_variant	Intron 31 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.2691-2916C>T		intron_variant	Intron 31 of 37	1	NM_018398.3	ENSP00000419101.1
CACNA2D3	ENST00000490478.5	c.2409-2916C>T		intron_variant	Intron 30 of 36	1		ENSP00000417279.1
CACNA2D3	ENST00000471363.5	n.*769-2916C>T		intron_variant	Intron 28 of 34	1		ENSP00000418228.1
CACNA2D3	ENST00000478261.5	n.77-2916C>T		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59493 AN: 151916 Hom.: 12424 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.392 AC: 59566 AN: 152034 Hom.: 12449 Cov.: 32 AF XY: 0.391 AC XY: 29024 AN XY: 74316

African (AFR) AF: 0.551 AC: 22842 AN: 41444

American (AMR) AF: 0.381 AC: 5818 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1769 AN: 5156

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4824

European-Finnish (FIN) AF: 0.358 AC: 3780 AN: 10564

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

European-Non Finnish (NFE) AF: 0.321 AC: 21806 AN: 67972

Other (OTH) AF: 0.352 AC: 744 AN: 2114

Alfa AF: 0.340 Hom.: 40488

Bravo AF: 0.402

Asia WGS AF: 0.350 AC: 1217 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		0.17
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

Publications

LitVar

Other links and lift over

dbSNP: rs4955826; hg19: chr3-55035874;