rs17053501

Positions:

chr3-53770462-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000720.4(CACNA1D):c.4014C>T(p.Phe1338=) variant causes a synonymous change. The variant allele was found at a frequency of 0.031 in 1,613,542 control chromosomes in the GnomAD database, including 1,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 174 hom., cov: 33)

Exomes 𝑓: 0.030 ( 830 hom. )

Consequence

CACNA1D
NM_000720.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.00

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 3-53770462-C-T is Benign according to our data. Variant chr3-53770462-C-T is described in ClinVar as [Benign]. Clinvar id is 226475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-53770462-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1D	NM_000720.4 linkuse as main transcript	c.4014C>T	p.Phe1338=	synonymous_variant	33/49	ENST00000288139.11
CACNA1D	NM_001128840.3 linkuse as main transcript	c.3954C>T	p.Phe1318=	synonymous_variant	32/48	ENST00000350061.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1D	ENST00000288139.11 linkuse as main transcript	c.4014C>T	p.Phe1338=	synonymous_variant	33/49	1	NM_000720.4	P2	Q01668-2
CACNA1D	ENST00000350061.11 linkuse as main transcript	c.3954C>T	p.Phe1318=	synonymous_variant	32/48	1	NM_001128840.3		Q01668-1

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6284

AN:

152130

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.00635

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0295

Gnomad OTH

AF:

0.0631

GnomAD3 exomes

AF:

0.0327

AC:

8222

AN:

251494

Hom.:

225

AF XY:

0.0331

AC XY:

4504

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0737

Gnomad AMR exome

AF:

0.0380

Gnomad ASJ exome

AF:

0.0518

Gnomad EAS exome

AF:

0.00767

Gnomad SAS exome

AF:

0.0429

Gnomad FIN exome

AF:

0.00531

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0366

GnomAD4 exome

AF:

0.0299

AC:

43727

AN:

1461294

Hom.:

830

Cov.:

AF XY:

0.0304

AC XY:

22127

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.0772

Gnomad4 AMR exome

AF:

0.0397

Gnomad4 ASJ exome

AF:

0.0497

Gnomad4 EAS exome

AF:

0.00494

Gnomad4 SAS exome

AF:

0.0431

Gnomad4 FIN exome

AF:

0.00534

Gnomad4 NFE exome

AF:

0.0282

Gnomad4 OTH exome

AF:

0.0346

GnomAD4 genome

AF:

0.0414

AC:

6296

AN:

152248

Hom.:

174

Cov.:

AF XY:

0.0405

AC XY:

3016

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.0434

Gnomad4 ASJ

AF:

0.0588

Gnomad4 EAS

AF:

0.00656

Gnomad4 SAS

AF:

0.0360

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.0295

Gnomad4 OTH

AF:

0.0629

Alfa

AF:

0.0349

Hom.:

255

Bravo

AF:

0.0463

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0377

EpiControl

AF:

0.0380

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 11, 2019	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Phe1338Phe in exon 33 of CACNA1D: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 7.1% (314/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17053501). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aldosterone-producing adenoma with seizures and neurological abnormalities

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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