Genetic Variant CADPS:c.2728-73G>A (chr3-62492519-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003716.4(CADPS):c.2728-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,426,362 control chromosomes in the GnomAD database, including 9,215 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 0.13 ( 1537 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7678 hom. )

Consequence

CADPS
NM_003716.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.538

Publications

9 publications found

Variant links:

Genes affected

CADPS (HGNC:1426): (calcium dependent secretion activator) This gene encodes a novel neural/endocrine-specific cytosolic and peripheral membrane protein required for the Ca2+-regulated exocytosis of secretory vesicles. The protein acts at a stage in exocytosis that follows ATP-dependent priming, which involves the essential synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Alternative splicing has been observed at this locus and three variants, encoding distinct isoforms, are described. [provided by RefSeq, Aug 2008]

CADPS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003716.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CADPS	NM_003716.4	MANE Select	c.2728-73G>A	intron	N/A	NP_003707.2
CADPS	NM_001438347.1		c.2788-73G>A	intron	N/A	NP_001425276.1
CADPS	NM_001438348.1		c.2776-73G>A	intron	N/A	NP_001425277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CADPS	ENST00000383710.9	TSL:1 MANE Select	c.2728-73G>A	intron	N/A	ENSP00000373215.4
CADPS	ENST00000612439.4	TSL:1	c.2848-73G>A	intron	N/A	ENSP00000484365.1
CADPS	ENST00000283269.13	TSL:1	c.2758-73G>A	intron	N/A	ENSP00000283269.9

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19789

AN:

152012

Hom.:

1527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.0703

Gnomad FIN

AF:

0.0631

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0958

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.101

AC:

129267

AN:

1274232

Hom.:

7678

AF XY:

0.0998

AC XY:

63519

AN XY:

636598

show subpopulations

African (AFR)

AF:

0.200

AC:

5865

AN:

29254

American (AMR)

AF:

0.289

AC:

11755

AN:

40608

Ashkenazi Jewish (ASJ)

AF:

0.0737

AC:

1664

AN:

22584

East Asian (EAS)

AF:

0.0507

AC:

1953

AN:

38506

South Asian (SAS)

AF:

0.0764

AC:

5860

AN:

76654

European-Finnish (FIN)

AF:

0.0685

AC:

3537

AN:

51608

Middle Eastern (MID)

AF:

0.0859

AC:

449

AN:

5230

European-Non Finnish (NFE)

AF:

0.0969

AC:

92698

AN:

956278

Other (OTH)

AF:

0.103

AC:

5486

AN:

53510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5534

11068

16602

22136

27670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3420

6840

10260

13680

17100

<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:

0.130

AC:

19833

AN:

152130

Hom.:

1537

Cov.:

AF XY:

0.130

AC XY:

9643

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.196

AC:

8114

AN:

41472

American (AMR)

AF:

0.215

AC:

3291

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

237

AN:

3470

East Asian (EAS)

AF:

0.0513

AC:

265

AN:

5168

South Asian (SAS)

AF:

0.0705

AC:

340

AN:

4820

European-Finnish (FIN)

AF:

0.0631

AC:

669

AN:

10604

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0958

AC:

6513

AN:

67998

Other (OTH)

AF:

0.119

AC:

251

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

863

1726

2590

3453

4316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.110

Hom.:

4250

Bravo

AF:

0.146

Asia WGS

AF:

0.0910

AC:

317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.12

(source)

DANN

Benign

0.75

PhyloP100

-0.54

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