chr3-55031657-C-T

Variant names:

• chr3-55031657-C-T
• rs3773555
• NM_018398.3:c.2987+13340C>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.2987+13340C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,076 control chromosomes in the GnomAD database, including 2,144 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 0.17 (2144 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.2987+13340C>T		intron_variant	Intron 35 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.2987+13340C>T		intron_variant	Intron 35 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25205 AN: 151958 Hom.: 2139 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.166 AC: 25239 AN: 152076 Hom.: 2144 Cov.: 32 AF XY: 0.169 AC XY: 12571 AN XY: 74346

African (AFR) AF: 0.146 AC: 6071 AN: 41488

American (AMR) AF: 0.184 AC: 2807 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3472

East Asian (EAS) AF: 0.0780 AC: 402 AN: 5152

South Asian (SAS) AF: 0.169 AC: 815 AN: 4822

European-Finnish (FIN) AF: 0.260 AC: 2755 AN: 10578

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11375 AN: 67970

Other (OTH) AF: 0.146 AC: 309 AN: 2114

Alfa AF: 0.161 Hom.: 3560

Bravo AF: 0.157

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		0.84
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: rs3773555; hg19: chr3-55065684;