rs1449325

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018398.3(CACNA2D3):​c.322-26376T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,112 control chromosomes in the GnomAD database, including 17,308 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 0.46 ( 17308 hom., cov: 32)

Consequence

CACNA2D3
NM_018398.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.631
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA2D3NM_018398.3 linkuse as main transcriptc.322-26376T>C intron_variant ENST00000474759.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA2D3ENST00000474759.6 linkuse as main transcriptc.322-26376T>C intron_variant 1 NM_018398.3 P1Q8IZS8-1

Frequencies

GnomAD3 genomes
AF:
0.464
AC:
70556
AN:
151994
Hom.:
17312
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.305
Gnomad AMI
AF:
0.436
Gnomad AMR
AF:
0.427
Gnomad ASJ
AF:
0.423
Gnomad EAS
AF:
0.432
Gnomad SAS
AF:
0.549
Gnomad FIN
AF:
0.568
Gnomad MID
AF:
0.513
Gnomad NFE
AF:
0.551
Gnomad OTH
AF:
0.495
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.464
AC:
70567
AN:
152112
Hom.:
17308
Cov.:
32
AF XY:
0.465
AC XY:
34589
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.305
Gnomad4 AMR
AF:
0.426
Gnomad4 ASJ
AF:
0.423
Gnomad4 EAS
AF:
0.432
Gnomad4 SAS
AF:
0.548
Gnomad4 FIN
AF:
0.568
Gnomad4 NFE
AF:
0.551
Gnomad4 OTH
AF:
0.490
Alfa
AF:
0.481
Hom.:
2903
Bravo
AF:
0.445
Asia WGS
AF:
0.427
AC:
1486
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.33
DANN
Benign
0.81

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1449325; hg19: chr3-54394366; API