3-54879327-CTTTTT-CTTTT

Variant names:

• chr3-54879327-CT-C
• rs35536476
• NM_018398.3:c.1783-9delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018398.3(CACNA2D3):​c.1783-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (10627 hom., cov: 0)
  • Exomes 𝑓: 0.42 (9512 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 1 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]

CACNA2D3-AS1 (HGNC:40702): (CACNA2D3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018398.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	NM_018398.3	MANE Select	c.1783-9delT		intron	N/A	NP_060868.2	Q8IZS8-1
	CACNA2D3-AS1	NR_046666.1		n.534-384delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.1783-22delT		intron	N/A	ENSP00000419101.1	Q8IZS8-1
	CACNA2D3	ENST00000490478.5	TSL:1	c.1501-22delT		intron	N/A	ENSP00000417279.1	Q8IZS8-2
	CACNA2D3	ENST00000468658.1	TSL:1	n.*1197-22delT		intron	N/A	ENSP00000417455.1	F8WAV4

Frequencies

GnomAD3 genomes AF: 0.374 AC: 53743 AN: 143602 Hom.: 10622 Cov.: 0

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.474 AC: 75129 AN: 158340 AF XY: 0.475

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.510

Gnomad FIN exome AF: 0.484

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.470

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.415 AC: 473151 AN: 1139152 Hom.: 9512 Cov.: 0 AF XY: 0.418 AC XY: 237800 AN XY: 568762

African (AFR) AF: 0.373 AC: 9384 AN: 25148

American (AMR) AF: 0.485 AC: 15287 AN: 31490

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 9521 AN: 21182

East Asian (EAS) AF: 0.517 AC: 17787 AN: 34398

South Asian (SAS) AF: 0.450 AC: 30938 AN: 68706

European-Finnish (FIN) AF: 0.455 AC: 18267 AN: 40116

Middle Eastern (MID) AF: 0.422 AC: 1896 AN: 4490

European-Non Finnish (NFE) AF: 0.404 AC: 349846 AN: 866386

Other (OTH) AF: 0.428 AC: 20225 AN: 47236

GnomAD4 genome AF: 0.374 AC: 53750 AN: 143638 Hom.: 10627 Cov.: 0 AF XY: 0.388 AC XY: 27014 AN XY: 69560

African (AFR) AF: 0.289 AC: 11285 AN: 39068

American (AMR) AF: 0.520 AC: 7564 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1474 AN: 3372

East Asian (EAS) AF: 0.807 AC: 4028 AN: 4992

South Asian (SAS) AF: 0.502 AC: 2257 AN: 4492

European-Finnish (FIN) AF: 0.461 AC: 3908 AN: 8476

Middle Eastern (MID) AF: 0.371 AC: 103 AN: 278

European-Non Finnish (NFE) AF: 0.337 AC: 22088 AN: 65534

Other (OTH) AF: 0.377 AC: 750 AN: 1988

Alfa AF: 0.259 Hom.: 445

Bravo AF: 0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
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: rs35536476; hg19: chr3-54913354;