3-53503852-T-C

Position:

• chr3-53503852-T-C

Variant summary

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

The NM_000720.4(CACNA1D):​c.483+2132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,704 control chromosomes in the GnomAD database, including 8,843 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 0.34 (8843 hom., cov: 30)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1D	NM_000720.4	c.483+2132T>C		intron_variant		ENST00000288139.11
CACNA1D	NM_001128840.3	c.483+2132T>C		intron_variant		ENST00000350061.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1D	ENST00000288139.11	c.483+2132T>C		intron_variant		1	NM_000720.4	P2
CACNA1D	ENST00000350061.11	c.483+2132T>C		intron_variant		1	NM_001128840.3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50830 AN: 151586 Hom.: 8830 Cov.: 30

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.335 AC: 50864 AN: 151704 Hom.: 8843 Cov.: 30 AF XY: 0.336 AC XY: 24939 AN XY: 74116

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.350

Alfa AF: 0.353 Hom.: 20479

Bravo AF: 0.341

Asia WGS AF: 0.300 AC: 1048 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	9.1
DANN	Benign	0.66

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: rs6763768; hg19: chr3-53537879;