rs147336902

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001128840.3(CACNA1D):c.954G>A(p.Ala318Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,614,136 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 39 hom. )

Consequence

CACNA1D
NM_001128840.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.538

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 3-53666373-G-A is Benign according to our data. Variant chr3-53666373-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 226481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-53666373-G-A is described in Lovd as [Benign]. Variant chr3-53666373-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.538 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00393 (599/152294) while in subpopulation NFE AF= 0.00637 (433/68020). AF 95% confidence interval is 0.00587. There are 4 homozygotes in gnomad4. There are 273 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1D	NM_000720.4 link	c.954G>A	p.Ala318Ala	synonymous_variant	Exon 7 of 49	ENST00000288139.11	NP_000711.1	Q01668-2Q59GD8
CACNA1D	NM_001128840.3 link	c.954G>A	p.Ala318Ala	synonymous_variant	Exon 7 of 48	ENST00000350061.11	NP_001122312.1	Q01668-1Q59GD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11 link	c.954G>A	p.Ala318Ala	synonymous_variant	Exon 7 of 49	1	NM_000720.4	ENSP00000288139.3		Q01668-2
CACNA1D	ENST00000350061.11 link	c.954G>A	p.Ala318Ala	synonymous_variant	Exon 7 of 48	1	NM_001128840.3	ENSP00000288133.5		Q01668-1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00637

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00412

AC:

1035

AN:

251416

Hom.:

AF XY:

0.00442

AC XY:

601

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00617

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00571

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00524

AC:

7665

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

3900

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00674

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00588

Gnomad4 OTH exome

AF:

0.00392

GnomAD4 genome

AF:

0.00393

AC:

599

AN:

152294

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

273

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00637

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00524

Hom.:

Bravo

AF:

0.00347

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00551

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Feb 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 05, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CACNA1D: BP4, BP7, BS2 -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 18, 2021

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala318Ala in exon 7 of CACNA1D: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.6% (52/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs147336902). -

Aldosterone-producing adenoma with seizures and neurological abnormalities

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sinoatrial node dysfunction and deafness;C3809609:Aldosterone-producing adenoma with seizures and neurological abnormalities

Benign:1

Sep 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CACNA1D-related disorder

Benign:1

Jul 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over