rs1075354

Variant names:

• chr3-54850531-A-G
• rs1075354
• NM_018398.3:c.1626+4064A>G

Variant summary

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

The NM_018398.3(CACNA2D3):​c.1626+4064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,016 control chromosomes in the GnomAD database, including 20,599 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 0.50 (20599 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.1626+4064A>G		intron_variant	Intron 17 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.1626+4064A>G		intron_variant	Intron 17 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75637 AN: 151898 Hom.: 20606 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.498 AC: 75631 AN: 152016 Hom.: 20599 Cov.: 32 AF XY: 0.481 AC XY: 35773 AN XY: 74306

African (AFR) AF: 0.392 AC: 16261 AN: 41454

American (AMR) AF: 0.396 AC: 6044 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3468

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5178

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4812

European-Finnish (FIN) AF: 0.480 AC: 5070 AN: 10554

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.625 AC: 42489 AN: 67964

Other (OTH) AF: 0.485 AC: 1022 AN: 2108

Alfa AF: 0.583 Hom.: 53408

Bravo AF: 0.486

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		0.091
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: rs1075354; hg19: chr3-54884558;