Genetic Variant NM_003716.4:c.1325+20154G>A (chr3-62625568-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.1325+20154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 150,602 control chromosomes in the GnomAD database, including 66,396 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 0.93 ( 66386 hom., cov: 31)

Exomes 𝑓: 0.92 ( 10 hom. )

Consequence

CADPS
NM_003716.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0910

Publications

3 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:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.1325+20154G>A	intron	N/A	NP_003707.2
CADPS	NM_001438347.1		c.1325+20154G>A	intron	N/A	NP_001425276.1
CADPS	NM_001438348.1		c.1325+20154G>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.1325+20154G>A	intron	N/A	ENSP00000373215.4
CADPS	ENST00000612439.4	TSL:1	c.1325+20154G>A	intron	N/A	ENSP00000484365.1
CADPS	ENST00000283269.13	TSL:1	c.1325+20154G>A	intron	N/A	ENSP00000283269.9

Frequencies

GnomAD3 genomes

AF:

0.934

AC:

140564

AN:

150462

Hom.:

66346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

0.952

Gnomad AMR

AF:

0.967

Gnomad ASJ

AF:

0.979

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.961

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.966

Gnomad OTH

AF:

0.940

GnomAD4 exome

AF:

0.917

AC:

AN:

Hom.:

Cov.:

AF XY:

0.909

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.950

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.934

AC:

140657

AN:

150578

Hom.:

66386

Cov.:

AF XY:

0.936

AC XY:

68889

AN XY:

73606

show subpopulations

African (AFR)

AF:

0.841

AC:

33600

AN:

39938

American (AMR)

AF:

0.967

AC:

14738

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

3399

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5167

AN:

5172

South Asian (SAS)

AF:

0.961

AC:

4629

AN:

4816

European-Finnish (FIN)

AF:

0.968

AC:

10280

AN:

10618

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

0.966

AC:

65710

AN:

68024

Other (OTH)

AF:

0.941

AC:

1974

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

402

804

1207

1609

2011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.957

Hom.:

180126

Bravo

AF:

0.931

Asia WGS

AF:

0.959

AC:

3337

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.4

(source)

DANN

Benign

0.48

PhyloP100

0.091

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over