rs1599231

Variant names:

• chr3-53685463-A-C
• rs1599231
• NM_000720.4:c.1220+11647A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-53685463-A-C
• chr3-53685463-A-G
• chr3-53685463-A-T

Variant summary

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

The NM_000720.4(CACNA1D):​c.1220+11647A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,120 control chromosomes in the GnomAD database, including 40,203 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 0.71 (40203 hom., cov: 33)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1D	NM_000720.4	c.1220+11647A>C		intron_variant	Intron 8 of 48	ENST00000288139.11	NP_000711.1
CACNA1D	NM_001128840.3	c.1220+12337A>C		intron_variant	Intron 8 of 47	ENST00000350061.11	NP_001122312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11	c.1220+11647A>C		intron_variant	Intron 8 of 48	1	NM_000720.4	ENSP00000288139.3
CACNA1D	ENST00000350061.11	c.1220+12337A>C		intron_variant	Intron 8 of 47	1	NM_001128840.3	ENSP00000288133.5

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108465 AN: 152002 Hom.: 40137 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.714 AC: 108591 AN: 152120 Hom.: 40203 Cov.: 33 AF XY: 0.722 AC XY: 53692 AN XY: 74358

African (AFR) AF: 0.888 AC: 36919 AN: 41564

American (AMR) AF: 0.719 AC: 10981 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2031 AN: 3466

East Asian (EAS) AF: 0.940 AC: 4874 AN: 5186

South Asian (SAS) AF: 0.763 AC: 3682 AN: 4828

European-Finnish (FIN) AF: 0.706 AC: 7461 AN: 10570

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40368 AN: 67912

Other (OTH) AF: 0.663 AC: 1401 AN: 2112

Alfa AF: 0.687 Hom.: 10867

Bravo AF: 0.722

Asia WGS AF: 0.858 AC: 2978 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		-0.46
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: rs1599231; hg19: chr3-53719490;