3-53673826-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128840.3(CACNA1D):c.1220+700C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,571,500 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 152 hom. )

Consequence

CACNA1D
NM_001128840.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.77

Publications

1 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, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
sinoatrial node dysfunction and deafness
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

CACNA1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 3-53673826-C-T is Benign according to our data. Variant chr3-53673826-C-T is described in ClinVar as Benign. ClinVar VariationId is 226468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128840.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNA1D	NM_000720.4	MANE Plus Clinical	c.1220+10C>T	intron	N/A	NP_000711.1	Q01668-2
CACNA1D	NM_001128840.3	MANE Select	c.1220+700C>T	intron	N/A	NP_001122312.1	Q01668-1
CACNA1D	NM_001128839.3		c.1220+700C>T	intron	N/A	NP_001122311.1	Q01668-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNA1D	ENST00000288139.11	TSL:1 MANE Plus Clinical	c.1220+10C>T	intron	N/A	ENSP00000288139.3	Q01668-2
CACNA1D	ENST00000350061.11	TSL:1 MANE Select	c.1220+700C>T	intron	N/A	ENSP00000288133.5	Q01668-1
CACNA1D	ENST00000481478.2	TSL:1	c.1220+700C>T	intron	N/A	ENSP00000418014.2	H0Y879

Frequencies

GnomAD3 genomes

AF:

0.00424

AC:

645

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0847

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00963

AC:

2422

AN:

251482

AF XY:

0.0101

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.0899

Gnomad FIN exome

AF:

0.00420

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00385

AC:

5469

AN:

1419218

Hom.:

152

Cov.:

AF XY:

0.00426

AC XY:

3022

AN XY:

708860

show subpopulations

African (AFR)

AF:

0.000245

AC:

AN:

32656

American (AMR)

AF:

0.000381

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.000851

AC:

AN:

25864

East Asian (EAS)

AF:

0.0766

AC:

3028

AN:

39554

South Asian (SAS)

AF:

0.0182

AC:

1558

AN:

85388

European-Finnish (FIN)

AF:

0.00386

AC:

206

AN:

53406

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.000218

AC:

234

AN:

1073022

Other (OTH)

AF:

0.00659

AC:

389

AN:

58992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

302

604

906

1208

1510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.00421

AC:

641

AN:

152282

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41560

American (AMR)

AF:

0.00216

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.0843

AC:

437

AN:

5182

South Asian (SAS)

AF:

0.0164

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68020

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000520

Hom.:

Bravo

AF:

0.00414

Asia WGS

AF:

0.0500

AC:

172

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Aldosterone-producing adenoma with seizures and neurological abnormalities (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over