3-53511427-G-C

Variant names:

• chr3-53511427-G-C
• rs312486
• NM_000720.4:c.483+9707G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000350061.11(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 ENST00000350061.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• aldosterone-producing adenoma with seizures and neurological abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• sinoatrial node dysfunction and deafness

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000350061.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1D	NM_000720.4	MANE Plus Clinical	c.483+9707G>C		intron	N/A	NP_000711.1
	CACNA1D	NM_001128840.3	MANE Select	c.483+9707G>C		intron	N/A	NP_001122312.1
	CACNA1D	NM_001128839.3		c.483+9707G>C		intron	N/A	NP_001122311.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1D	ENST00000288139.11	TSL:1 MANE Plus Clinical	c.483+9707G>C		intron	N/A	ENSP00000288139.3
	CACNA1D	ENST00000350061.11	TSL:1 MANE Select	c.483+9707G>C		intron	N/A	ENSP00000288133.5
	CACNA1D	ENST00000481478.2	TSL:1	c.483+9707G>C		intron	N/A	ENSP00000418014.2

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

African (AFR) AF: 0.820 AC: 34016 AN: 41498

American (AMR) AF: 0.818 AC: 12490 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2928 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4405 AN: 5166

South Asian (SAS) AF: 0.830 AC: 3999 AN: 4820

European-Finnish (FIN) AF: 0.830 AC: 8785 AN: 10578

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52711 AN: 67994

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.741 Hom.: 2522

Bravo AF: 0.803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs312486; hg19: chr3-53545454;