chr7-82218335-G-A

Position:

• chr7-82218335-G-A

Variant summary

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

The NM_000722.4(CACNA2D1):​c.295-47726C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,026 control chromosomes in the GnomAD database, including 6,481 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 0.26 (6481 hom., cov: 32)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.295-47726C>T		intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.295-47726C>T		intron_variant		1	NM_000722.4	ENSP00000349320

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40032 AN: 151908 Hom.: 6492 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.263 AC: 40007 AN: 152026 Hom.: 6481 Cov.: 32 AF XY: 0.261 AC XY: 19351 AN XY: 74282

Gnomad4 AFR AF: 0.0733

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.307

Alfa AF: 0.331 Hom.: 8308

Bravo AF: 0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.76

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: rs10954668; hg19: chr7-81847651; COSMIC: COSV62397350;