7-82156904-C-T

Position:

• chr7-82156904-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.354+13646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,954 control chromosomes in the GnomAD database, including 1,571 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 0.11 (1571 hom., cov: 33)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4	c.354+13646G>A		intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.354+13646G>A		intron_variant		1	NM_000722.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16709 AN: 151836 Hom.: 1566 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.110 AC: 16744 AN: 151954 Hom.: 1571 Cov.: 33 AF XY: 0.112 AC XY: 8289 AN XY: 74286

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0422 Hom.: 63

Bravo AF: 0.121

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.71

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: rs2367911; hg19: chr7-81786220;