rs258654

Positions:

• chr7-82093515-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.527-8615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,050 control chromosomes in the GnomAD database, including 49,964 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 0.81 (49964 hom., cov: 31)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.527-8615G>A		intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.527-8615G>A		intron_variant		1	NM_000722.4	ENSP00000349320

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123048 AN: 151932 Hom.: 49943 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.810 AC: 123121 AN: 152050 Hom.: 49964 Cov.: 31 AF XY: 0.808 AC XY: 60069 AN XY: 74328

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.808

Alfa AF: 0.807 Hom.: 9392

Bravo AF: 0.809

Asia WGS AF: 0.752 AC: 2613 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.30

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: rs258654; hg19: chr7-81722831;