rs75407252

Positions:

• chr3-54207859-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018398.3(CACNA2D3):​c.204+84265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 152,142 control chromosomes in the GnomAD database, including 55 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 0.015 (55 hom., cov: 33)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0146 (2226/152142) while in subpopulation AFR AF= 0.0502 (2084/41488). AF 95% confidence interval is 0.0484. There are 55 homozygotes in gnomad4. There are 1052 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.204+84265C>T		intron_variant		ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.204+84265C>T		intron_variant		1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2217 AN: 152024 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00957

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

GnomAD4 genome AF: 0.0146 AC: 2226 AN: 152142 Hom.: 55 Cov.: 33 AF XY: 0.0141 AC XY: 1052 AN XY: 74384

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.0102 Hom.: 7

Bravo AF: 0.0169

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.015
DANN	Benign	0.70

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: rs75407252; hg19: chr3-54241886;