rs61386831

Variant names:

• chr12-1885952-C-T
• rs61386831
• NM_172364.5:c.1068+13G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172364.5(CACNA2D4):​c.1068+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,600,026 control chromosomes in the GnomAD database, including 9,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1401 hom., cov: 31)
  • Exomes 𝑓: 0.10 (8255 hom.)
• Consequence: CACNA2D4 NM_172364.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.29

Genes affected

CACNA2D4 (HGNC:20202): (calcium voltage-gated channel auxiliary subunit alpha2delta 4) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

LOC124902858 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-1885952-C-T is Benign according to our data. Variant chr12-1885952-C-T is described in ClinVar as [Benign]. Clinvar id is 262808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D4	NM_172364.5	c.1068+13G>A		intron_variant	Intron 9 of 37	ENST00000382722.10	NP_758952.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D4	ENST00000382722.10	c.1068+13G>A		intron_variant	Intron 9 of 37	1	NM_172364.5	ENSP00000372169.4
CACNA2D4	ENST00000586184.5	c.1068+13G>A		intron_variant	Intron 9 of 36	5		ENSP00000465060.1
CACNA2D4	ENST00000587995.5	c.1068+13G>A		intron_variant	Intron 9 of 36	5		ENSP00000465372.1
CACNA2D4	ENST00000585708.5	c.876+13G>A		intron_variant	Intron 9 of 36	5		ENSP00000467697.1
CACNA2D4	ENST00000588077.5	c.876+13G>A		intron_variant	Intron 9 of 37	5		ENSP00000468530.1
CACNA2D4	ENST00000444595.6	n.1068+13G>A		intron_variant	Intron 9 of 36	1		ENSP00000403371.2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18606 AN: 151844 Hom.: 1392 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0305

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.0996 AC: 24360 AN: 244538 Hom.: 1394 AF XY: 0.102 AC XY: 13525 AN XY: 132472

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0336

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.0909

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.0997

GnomAD4 exome AF: 0.103 AC: 148529 AN: 1448064 Hom.: 8255 Cov.: 31 AF XY: 0.104 AC XY: 74660 AN XY: 720716

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.0508

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0420

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0908

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.123 AC: 18652 AN: 151962 Hom.: 1401 Cov.: 31 AF XY: 0.120 AC XY: 8880 AN XY: 74290

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0306

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0826

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.105

Alfa AF: 0.115 Hom.: 209

Bravo AF: 0.121

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal cone dystrophy 4 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.88

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: rs61386831; hg19: chr12-1995118; COSMIC: COSV54951187; COSMIC: COSV54951187;