NM_000720.4:c.1220+9141G>A

Variant names:

• chr3-53682957-G-A
• rs898408
• NM_000720.4:c.1220+9141G>A

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+9141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,092 control chromosomes in the GnomAD database, including 38,711 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 0.70 (38711 hom., cov: 32)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000720.4. 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.1220+9141G>A		intron	N/A	NP_000711.1
	CACNA1D	NM_001128840.3	MANE Select	c.1220+9831G>A		intron	N/A	NP_001122312.1
	CACNA1D	NM_001128839.3		c.1220+9831G>A		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.1220+9141G>A		intron	N/A	ENSP00000288139.3
	CACNA1D	ENST00000350061.11	TSL:1 MANE Select	c.1220+9831G>A		intron	N/A	ENSP00000288133.5
	CACNA1D	ENST00000481478.2	TSL:1	c.1220+9831G>A		intron	N/A	ENSP00000418014.2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106675 AN: 151972 Hom.: 38645 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.702 AC: 106804 AN: 152092 Hom.: 38711 Cov.: 32 AF XY: 0.710 AC XY: 52795 AN XY: 74338

African (AFR) AF: 0.857 AC: 35560 AN: 41488

American (AMR) AF: 0.716 AC: 10942 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2016 AN: 3464

East Asian (EAS) AF: 0.896 AC: 4632 AN: 5170

South Asian (SAS) AF: 0.754 AC: 3632 AN: 4820

European-Finnish (FIN) AF: 0.704 AC: 7449 AN: 10574

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

European-Non Finnish (NFE) AF: 0.593 AC: 40321 AN: 67982

Other (OTH) AF: 0.653 AC: 1380 AN: 2112

Alfa AF: 0.609 Hom.: 2327

Bravo AF: 0.709

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		-0.83
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: rs898408; hg19: chr3-53716984;