rs10490844

Positions:

• chr3-53812050-A-G

Variant summary

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

The NM_000720.4(CACNA1D):​c.*644A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 152,484 control chromosomes in the GnomAD database, including 109 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 0.026 (109 hom., cov: 33)
  • Exomes 𝑓: 0.017 (0 hom.)
• Consequence: CACNA1D NM_000720.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

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=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1D	NM_000720.4	c.*644A>G		3_prime_UTR_variant	49/49	ENST00000288139.11	NP_000711.1
CACNA1D	NM_001128840.3	c.*644A>G		3_prime_UTR_variant	48/48	ENST00000350061.11	NP_001122312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11	c.*644A>G		3_prime_UTR_variant	49/49	1	NM_000720.4	ENSP00000288139	P2
CACNA1D	ENST00000350061.11	c.*644A>G		3_prime_UTR_variant	48/48	1	NM_001128840.3	ENSP00000288133

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3955 AN: 152188 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0169 AC: 3 AN: 178 Hom.: 0 Cov.: 0 AF XY: 0.0182 AC XY: 2 AN XY: 110

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0260 AC: 3958 AN: 152306 Hom.: 109 Cov.: 33 AF XY: 0.0283 AC XY: 2105 AN XY: 74474

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0213 Hom.: 15

Bravo AF: 0.0255

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	7.3
DANN	Benign	0.86

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: rs10490844; hg19: chr3-53846077;