rs6967334

Positions:

• chr7-82432452-G-C
• chr7-82432452-G-T

Variant summary

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

The NM_000722.4(CACNA2D1):​c.95+10913C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,182 control chromosomes in the GnomAD database, including 8,027 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 0.29 (8027 hom., cov: 34)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.95+10913C>G		intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.95+10913C>G		intron_variant		1	NM_000722.4	ENSP00000349320
CACNA2D1	ENST00000423588.1	c.95+10913C>G		intron_variant		1		ENSP00000405395
CACNA2D1	ENST00000443883.2	c.95+10913C>G		intron_variant		5		ENSP00000409374	P1
CACNA2D1	ENST00000705962.1	c.11+10913C>G		intron_variant				ENSP00000516190

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44779 AN: 152062 Hom.: 8032 Cov.: 34

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.294 AC: 44776 AN: 152182 Hom.: 8027 Cov.: 34 AF XY: 0.298 AC XY: 22212 AN XY: 74412

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.311

Alfa AF: 0.228 Hom.: 604

Bravo AF: 0.268

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.50

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: rs6967334; hg19: chr7-82061768;