rs6967334

Variant names:

• chr7-82432452-G-C
• rs6967334
• NM_000722.4:c.95+10913C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• short QT syndrome

  Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
• Brugada syndrome

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• developmental and epileptic encephalopathy 110

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D1	NM_000722.4	MANE Select	c.95+10913C>G		intron	N/A	NP_000713.2
	CACNA2D1	NM_001366867.1		c.95+10913C>G		intron	N/A	NP_001353796.1
	CACNA2D1	NM_001302890.2		c.95+10913C>G		intron	N/A	NP_001289819.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D1	ENST00000356860.8	TSL:1 MANE Select	c.95+10913C>G		intron	N/A	ENSP00000349320.3
	CACNA2D1	ENST00000423588.1	TSL:1	c.95+10913C>G		intron	N/A	ENSP00000405395.1
	CACNA2D1	ENST00000443883.2	TSL:5	c.95+10913C>G		intron	N/A	ENSP00000409374.2

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

African (AFR) AF: 0.0922 AC: 3831 AN: 41552

American (AMR) AF: 0.253 AC: 3875 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2073 AN: 5162

South Asian (SAS) AF: 0.549 AC: 2648 AN: 4820

European-Finnish (FIN) AF: 0.403 AC: 4266 AN: 10584

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.383 AC: 26032 AN: 67978

Other (OTH) AF: 0.311 AC: 658 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6967334; hg19: chr7-82061768;