rs9311525

Positions:

• chr3-54149523-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018398.3(CACNA2D3):​c.204+25929G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,856 control chromosomes in the GnomAD database, including 17,299 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 0.47 (17299 hom., cov: 30)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D3	NM_018398.3	c.204+25929G>A		intron_variant		ENST00000474759.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.204+25929G>A		intron_variant		1	NM_018398.3	P1
CACNA2D3	ENST00000490478.5	c.-79+25929G>A		intron_variant		1
CACNA2D3	ENST00000471363.5	c.-79+25929G>A		intron_variant, NMD_transcript_variant		1
CACNA2D3	ENST00000477024.5	c.-79+25929G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71743 AN: 151736 Hom.: 17283 Cov.: 30

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.473 AC: 71790 AN: 151856 Hom.: 17299 Cov.: 30 AF XY: 0.474 AC XY: 35219 AN XY: 74260

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.459

Alfa AF: 0.440 Hom.: 18233

Bravo AF: 0.471

Asia WGS AF: 0.449 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.74

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: rs9311525; hg19: chr3-54183550;