rs2250736

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_000720.4(CACNA1D):c.1104T>C(p.Asp368Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,612,480 control chromosomes in the GnomAD database, including 260,082 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 33235 hom., cov: 32)

Exomes 𝑓: 0.55 ( 226847 hom. )

Consequence

CACNA1D
NM_000720.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.98

Publications

27 publications found

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 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)

CACNA1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 3-53666523-T-C is Benign according to our data. Variant chr3-53666523-T-C is described in ClinVar as Benign. ClinVar VariationId is 226467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CACNA1D	NM_000720.4	MANE Plus Clinical	c.1104T>C	p.Asp368Asp	synonymous	Exon 7 of 49	NP_000711.1
CACNA1D	NM_001128840.3	MANE Select	c.1104T>C	p.Asp368Asp	synonymous	Exon 7 of 48	NP_001122312.1
CACNA1D	NM_001128839.3		c.1104T>C	p.Asp368Asp	synonymous	Exon 7 of 46	NP_001122311.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CACNA1D	ENST00000288139.11	TSL:1 MANE Plus Clinical	c.1104T>C	p.Asp368Asp	synonymous	Exon 7 of 49	ENSP00000288139.3
CACNA1D	ENST00000350061.11	TSL:1 MANE Select	c.1104T>C	p.Asp368Asp	synonymous	Exon 7 of 48	ENSP00000288133.5
CACNA1D	ENST00000481478.2	TSL:1	c.1104T>C	p.Asp368Asp	synonymous	Exon 7 of 49	ENSP00000418014.2

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97722

AN:

151976

Hom.:

33179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.636

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.586

GnomAD2 exomes

AF:

0.588

AC:

147643

AN:

250970

AF XY:

0.583

show subpopulations

Gnomad AFR exome

AF:

0.888

Gnomad AMR exome

AF:

0.598

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.601

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.553

AC:

807057

AN:

1460384

Hom.:

226847

Cov.:

AF XY:

0.554

AC XY:

402673

AN XY:

726622

show subpopulations

African (AFR)

AF:

0.893

AC:

29878

AN:

33464

American (AMR)

AF:

0.596

AC:

26662

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.479

AC:

12523

AN:

26122

East Asian (EAS)

AF:

0.666

AC:

26449

AN:

39694

South Asian (SAS)

AF:

0.652

AC:

56182

AN:

86224

European-Finnish (FIN)

AF:

0.592

AC:

31638

AN:

53412

Middle Eastern (MID)

AF:

0.534

AC:

3078

AN:

5766

European-Non Finnish (NFE)

AF:

0.528

AC:

586391

AN:

1110626

Other (OTH)

AF:

0.568

AC:

34256

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18717

37435

56152

74870

93587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16956

33912

50868

67824

84780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.643

AC:

97838

AN:

152096

Hom.:

33235

Cov.:

AF XY:

0.646

AC XY:

48021

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.875

AC:

36339

AN:

41512

American (AMR)

AF:

0.587

AC:

8973

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

1681

AN:

3468

East Asian (EAS)

AF:

0.636

AC:

3284

AN:

5160

South Asian (SAS)

AF:

0.664

AC:

3197

AN:

4818

European-Finnish (FIN)

AF:

0.596

AC:

6297

AN:

10566

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36087

AN:

67972

Other (OTH)

AF:

0.582

AC:

1230

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1634

3269

4903

6538

8172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.562

Hom.:

40326

Bravo

AF:

0.651

Asia WGS

AF:

0.680

AC:

2364

AN:

3478

EpiCase

AF:

0.526

EpiControl

AF:

0.514

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Aldosterone-producing adenoma with seizures and neurological abnormalities (2)

not provided (2)

Sinoatrial node dysfunction and deafness (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

(source)

DANN

Benign

0.40

PhyloP100

-2.0

PromoterAI

0.071

Neutral

(source)

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over