7-82102130-C-T

Variant names:

• chr7-82102130-C-T
• rs258671
• NM_000722.4:c.526+14914G>A

Variant summary

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

The NM_000722.4(CACNA2D1):​c.526+14914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,324 control chromosomes in the GnomAD database, including 10,957 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 0.37 (10957 hom., cov: 31)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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]

LOC124901687 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.526+14914G>A		intron_variant	Intron 6 of 38	ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.526+14914G>A		intron_variant	Intron 6 of 38	1	NM_000722.4	ENSP00000349320.3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56716 AN: 151208 Hom.: 10961 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.375 AC: 56721 AN: 151324 Hom.: 10957 Cov.: 31 AF XY: 0.377 AC XY: 27850 AN XY: 73872

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.357

Alfa AF: 0.376 Hom.: 4882

Bravo AF: 0.364

Asia WGS AF: 0.359 AC: 1244 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.59
DANN	Benign	0.49

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: rs258671; hg19: chr7-81731446;