rs6950804

Positions:

• chr7-82198562-C-T

Variant summary

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

The NM_000722.4(CACNA2D1):​c.295-27953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,758 control chromosomes in the GnomAD database, including 6,528 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 0.27 (6528 hom., cov: 31)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

CACNA2D1 (HGNC:1399): (calcium voltage-gated channel auxiliary subunit alpha2delta 1) The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4	c.295-27953G>A		intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.295-27953G>A		intron_variant		1	NM_000722.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40723 AN: 151642 Hom.: 6510 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.269 AC: 40793 AN: 151758 Hom.: 6528 Cov.: 31 AF XY: 0.271 AC XY: 20135 AN XY: 74168

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.241

Alfa AF: 0.187 Hom.: 4694

Bravo AF: 0.281

Asia WGS AF: 0.233 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.68

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: rs6950804; hg19: chr7-81827878;