3-53423912-A-G

Variant names:

• chr3-53423912-A-G
• rs552486
• ENST00000637424.1:c.140-73240A>G

Variant summary

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

The ENST00000637424.1(CACNA1D):​c.140-73240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,104 control chromosomes in the GnomAD database, including 3,011 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 0.18 (3011 hom., cov: 32)
• Consequence: CACNA1D ENST00000637424.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

Genes affected

CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

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 = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000637424.1	c.140-73240A>G		intron_variant	Intron 1 of 46	5		ENSP00000489769.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27457 AN: 151986 Hom.: 3013 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.181 AC: 27462 AN: 152104 Hom.: 3011 Cov.: 32 AF XY: 0.187 AC XY: 13914 AN XY: 74356

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.201

Alfa AF: 0.174 Hom.: 303

Bravo AF: 0.174

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs552486; hg19: chr3-53457939;