rs10510764

Positions:

• chr3-53451763-C-G

Variant summary

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

The ENST00000637424.1(CACNA1D):​c.140-45389C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 152,294 control chromosomes in the GnomAD database, including 208 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 0.027 (208 hom., cov: 32)
• Consequence: CACNA1D ENST00000637424.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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 (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000637424.1	c.140-45389C>G		intron_variant		5		ENSP00000489769	A2

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 4144 AN: 152176 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.00579

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0272 AC: 4146 AN: 152294 Hom.: 208 Cov.: 32 AF XY: 0.0314 AC XY: 2340 AN XY: 74468

Gnomad4 AFR AF: 0.00577

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0187 Hom.: 6

Bravo AF: 0.0277

Asia WGS AF: 0.116 AC: 402 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	0.26
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10510764; hg19: chr3-53485790;