rs9311504

chr3-53536469-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000720.4(CACNA1D):c.483+34749A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 152,212 control chromosomes in the GnomAD database, including 2,193 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 0.099 (2193 hom., cov: 33)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1D	NM_000720.4	c.483+34749A>C		intron_variant		ENST00000288139.11
CACNA1D	NM_001128840.3	c.483+34749A>C		intron_variant		ENST00000350061.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1D	ENST00000288139.11	c.483+34749A>C		intron_variant		1	NM_000720.4	P2
CACNA1D	ENST00000350061.11	c.483+34749A>C		intron_variant		1	NM_001128840.3

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15041 AN: 152094 Hom.: 2186 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0754

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00620

Gnomad OTH AF: 0.0753

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

GnomAD4 genome AF: 0.0991 AC: 15079 AN: 152212 Hom.: 2193 Cov.: 33 AF XY: 0.0965 AC XY: 7188 AN XY: 74456

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.00348

Gnomad4 NFE AF: 0.00620

Gnomad4 OTH AF: 0.0745

Alfa AF: 0.0634 Hom.: 170

Bravo AF: 0.116

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	18
Dann	Benign	0.80

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: rs9311504; hg19: chr3-53570496;