3-54885601-A-T

Position:

• chr3-54885601-A-T

Variant summary

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

The ENST00000474759.6(CACNA2D3):​c.2056+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,597,892 control chromosomes in the GnomAD database, including 71 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 0.011 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (29 hom.)
• Consequence: CACNA2D3 ENST00000474759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

CACNA2D3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1713/152334) while in subpopulation AFR AF= 0.0391 (1625/41570). AF 95% confidence interval is 0.0375. There are 42 homozygotes in gnomad4. There are 793 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.2056+15A>T		intron_variant		ENST00000474759.6	NP_060868.2
CACNA2D3-AS1	NR_046666.1	n.534-6657T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.2056+15A>T		intron_variant		1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1709 AN: 152216 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00278 AC: 665 AN: 238986 Hom.: 12 AF XY: 0.00217 AC XY: 281 AN XY: 129322

Gnomad AFR exome AF: 0.0404

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000684

GnomAD4 exome AF: 0.00116 AC: 1679 AN: 1445558 Hom.: 29 Cov.: 28 AF XY: 0.00101 AC XY: 728 AN XY: 719204

Gnomad4 AFR exome AF: 0.0392

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.0000772

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000471

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000864

Gnomad4 OTH exome AF: 0.00261

GnomAD4 genome AF: 0.0112 AC: 1713 AN: 152334 Hom.: 42 Cov.: 32 AF XY: 0.0106 AC XY: 793 AN XY: 74502

Gnomad4 AFR AF: 0.0391

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00541 Hom.: 0

Bravo AF: 0.0128

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17054513; hg19: chr3-54919628;