chr3-53580457-C-A

Position:

• chr3-53580457-C-A

Variant summary

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

The NM_000720.4(CACNA1D):​c.484-70322C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,208 control chromosomes in the GnomAD database, including 47,869 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 0.79 (47869 hom., cov: 33)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1D	NM_000720.4	c.484-70322C>A		intron_variant		ENST00000288139.11	NP_000711.1
CACNA1D	NM_001128840.3	c.484-70322C>A		intron_variant		ENST00000350061.11	NP_001122312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11	c.484-70322C>A		intron_variant		1	NM_000720.4	ENSP00000288139	P2
CACNA1D	ENST00000350061.11	c.484-70322C>A		intron_variant		1	NM_001128840.3	ENSP00000288133

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120438 AN: 152090 Hom.: 47826 Cov.: 33

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.792 AC: 120545 AN: 152208 Hom.: 47869 Cov.: 33 AF XY: 0.794 AC XY: 59120 AN XY: 74418

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.774

Alfa AF: 0.807 Hom.: 44503

Bravo AF: 0.784

Asia WGS AF: 0.794 AC: 2763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.48

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: rs709323; hg19: chr3-53614484;