3-54387228-T-C

Variant names:

• chr3-54387228-T-C
• rs1868505
• NM_018398.3:c.381+454T>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.381+454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,298 control chromosomes in the GnomAD database, including 56,931 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 0.86 (56931 hom., cov: 34)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.381+454T>C		intron_variant	Intron 4 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.381+454T>C		intron_variant	Intron 4 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131533 AN: 152180 Hom.: 56899 Cov.: 34

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.864 AC: 131617 AN: 152298 Hom.: 56931 Cov.: 34 AF XY: 0.864 AC XY: 64351 AN XY: 74466

African (AFR) AF: 0.881 AC: 36609 AN: 41568

American (AMR) AF: 0.851 AC: 13003 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2905 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4249 AN: 5186

South Asian (SAS) AF: 0.828 AC: 3993 AN: 4824

European-Finnish (FIN) AF: 0.870 AC: 9227 AN: 10610

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58762 AN: 68034

Other (OTH) AF: 0.865 AC: 1826 AN: 2110

Alfa AF: 0.856 Hom.: 28201

Bravo AF: 0.865

Asia WGS AF: 0.817 AC: 2841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.81
PhyloP100		-0.12
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: rs1868505; hg19: chr3-54421255;