chr3-55012075-G-A

Variant names:

• chr3-55012075-G-A
• rs4955917
• NM_018398.3:c.2875+2632G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018398.3(CACNA2D3):​c.2875+2632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,120 control chromosomes in the GnomAD database, including 38,123 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 0.70 (38123 hom., cov: 33)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.2875+2632G>A		intron_variant	Intron 34 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.2875+2632G>A		intron_variant	Intron 34 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106969 AN: 152002 Hom.: 38104 Cov.: 33

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.704 AC: 107044 AN: 152120 Hom.: 38123 Cov.: 33 AF XY: 0.700 AC XY: 52071 AN XY: 74364

African (AFR) AF: 0.736 AC: 30523 AN: 41482

American (AMR) AF: 0.693 AC: 10599 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2230 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5168

South Asian (SAS) AF: 0.573 AC: 2761 AN: 4820

European-Finnish (FIN) AF: 0.760 AC: 8048 AN: 10586

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48595 AN: 67996

Other (OTH) AF: 0.682 AC: 1437 AN: 2108

Alfa AF: 0.704 Hom.: 162119

Bravo AF: 0.699

Asia WGS AF: 0.495 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.48
PhyloP100		-1.1
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: rs4955917; hg19: chr3-55046102;