chr3-54708535-A-G

Variant names:

• chr3-54708535-A-G
• rs608142
• NM_018398.3:c.1168-44064A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018398.3(CACNA2D3):​c.1168-44064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,230 control chromosomes in the GnomAD database, including 63,986 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 0.91 (63986 hom., cov: 32)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 5 publications found

Genes affected

CACNA2D3 (HGNC:15460): (calcium voltage-gated channel auxiliary subunit alpha2delta 3) 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.1168-44064A>G		intron_variant	Intron 11 of 37	ENST00000474759.6	NP_060868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.1168-44064A>G		intron_variant	Intron 11 of 37	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139172 AN: 152112 Hom.: 63930 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.906

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

GnomAD4 genome AF: 0.915 AC: 139290 AN: 152230 Hom.: 63986 Cov.: 32 AF XY: 0.911 AC XY: 67789 AN XY: 74408

African (AFR) AF: 0.937 AC: 38926 AN: 41550

American (AMR) AF: 0.928 AC: 14203 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3199 AN: 3472

East Asian (EAS) AF: 0.617 AC: 3186 AN: 5162

South Asian (SAS) AF: 0.846 AC: 4075 AN: 4818

European-Finnish (FIN) AF: 0.902 AC: 9557 AN: 10590

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.928 AC: 63138 AN: 68024

Other (OTH) AF: 0.905 AC: 1910 AN: 2110

Alfa AF: 0.924 Hom.: 41352

Bravo AF: 0.918

Asia WGS AF: 0.775 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.51
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs608142; hg19: chr3-54742562; COSMIC: COSV55563745;