3-53685463-A-C

Position:

• chr3-53685463-A-C

Variant summary

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

The NM_000720.4(CACNA1D):​c.1220+11647A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,120 control chromosomes in the GnomAD database, including 40,203 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 0.71 (40203 hom., cov: 33)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1D	NM_000720.4	c.1220+11647A>C		intron_variant		ENST00000288139.11
CACNA1D	NM_001128840.3	c.1220+12337A>C		intron_variant		ENST00000350061.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1D	ENST00000288139.11	c.1220+11647A>C		intron_variant		1	NM_000720.4	P2
CACNA1D	ENST00000350061.11	c.1220+12337A>C		intron_variant		1	NM_001128840.3

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108465 AN: 152002 Hom.: 40137 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.714 AC: 108591 AN: 152120 Hom.: 40203 Cov.: 33 AF XY: 0.722 AC XY: 53692 AN XY: 74358

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.663

Alfa AF: 0.674 Hom.: 4450

Bravo AF: 0.722

Asia WGS AF: 0.858 AC: 2978 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.68

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: rs1599231; hg19: chr3-53719490;