rs925019

Positions:

• chr3-62727376-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003716.4(CADPS):​c.888+26065C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,712 control chromosomes in the GnomAD database, including 4,411 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 0.23 (4411 hom., cov: 33)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS	NM_003716.4	c.888+26065C>A		intron_variant		ENST00000383710.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS	ENST00000383710.9	c.888+26065C>A		intron_variant		1	NM_003716.4	P2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34376 AN: 151592 Hom.: 4405 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34397 AN: 151712 Hom.: 4411 Cov.: 33 AF XY: 0.225 AC XY: 16664 AN XY: 74158

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.230

Alfa AF: 0.222 Hom.: 1844

Bravo AF: 0.227

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs925019; hg19: chr3-62713051;