rs11978472

Positions:

• chr7-82210237-A-C
• chr7-82210237-A-G
• chr7-82210237-A-T

Variant summary

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

The NM_000722.4(CACNA2D1):​c.295-39628T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,998 control chromosomes in the GnomAD database, including 9,790 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 0.33 (9790 hom., cov: 32)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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]

CACNA2D1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.295-39628T>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.295-39628T>G		intron_variant		1	NM_000722.4	ENSP00000349320.3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50161 AN: 151880 Hom.: 9787 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.330 AC: 50180 AN: 151998 Hom.: 9790 Cov.: 32 AF XY: 0.337 AC XY: 25061 AN XY: 74290

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.292

Alfa AF: 0.352 Hom.: 4265

Bravo AF: 0.306

Asia WGS AF: 0.422 AC: 1465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.86

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: rs11978472; hg19: chr7-81839553;