chr3-54894147-A-C

Position:

• chr3-54894147-A-C

Variant summary

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

The NM_018398.3(CACNA2D3):​c.2247-2602A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,030 control chromosomes in the GnomAD database, including 36,289 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 0.69 (36289 hom., cov: 31)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.2247-2602A>C		intron_variant		ENST00000474759.6	NP_060868.2
CACNA2D3-AS1	NR_046666.1	n.533+466T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.2247-2602A>C		intron_variant		1	NM_018398.3	ENSP00000419101	P1
CACNA2D3	ENST00000490478.5	c.1965-2602A>C		intron_variant		1		ENSP00000417279
CACNA2D3	ENST00000471363.5	c.*325-2602A>C		intron_variant, NMD_transcript_variant		1		ENSP00000418228
CACNA2D3-AS1	ENST00000471265.1	n.533+466T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104520 AN: 151912 Hom.: 36285 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.688 AC: 104567 AN: 152030 Hom.: 36289 Cov.: 31 AF XY: 0.693 AC XY: 51511 AN XY: 74322

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.703

Alfa AF: 0.690 Hom.: 46634

Bravo AF: 0.691

Asia WGS AF: 0.770 AC: 2675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.75
DANN	Benign	0.53

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: rs10510775; hg19: chr3-54928174;