3-53511427-G-C

Position:

• chr3-53511427-G-C

Variant summary

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

The NM_001128840.3(CACNA1D):​c.483+9707G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,114 control chromosomes in the GnomAD database, including 48,906 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 0.80 (48906 hom., cov: 31)
• Consequence: CACNA1D NM_001128840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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]

CACNA1D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1D	NM_000720.4	c.483+9707G>C		intron_variant		ENST00000288139.11	NP_000711.1
CACNA1D	NM_001128840.3	c.483+9707G>C		intron_variant		ENST00000350061.11	NP_001122312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11	c.483+9707G>C		intron_variant		1	NM_000720.4	ENSP00000288139.3
CACNA1D	ENST00000350061.11	c.483+9707G>C		intron_variant		1	NM_001128840.3	ENSP00000288133.5

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121717 AN: 151996 Hom.: 48859 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.801 AC: 121817 AN: 152114 Hom.: 48906 Cov.: 31 AF XY: 0.805 AC XY: 59847 AN XY: 74346

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.783

Alfa AF: 0.741 Hom.: 2522

Bravo AF: 0.803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.36

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: rs312486; hg19: chr3-53545454;