rs17637119

chr3-62450046-G-A

Variant summary

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

The NM_003716.4(CADPS):c.3637-4249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,122 control chromosomes in the GnomAD database, including 1,227 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 0.11 (1227 hom., cov: 32)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS	NM_003716.4	c.3637-4249C>T		intron_variant		ENST00000383710.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS	ENST00000383710.9	c.3637-4249C>T		intron_variant		1	NM_003716.4	P2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16747 AN: 152002 Hom.: 1224 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.110 AC: 16763 AN: 152122 Hom.: 1227 Cov.: 32 AF XY: 0.113 AC XY: 8414 AN XY: 74360

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0621

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.107

Alfa AF: 0.133 Hom.: 745

Bravo AF: 0.103

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.37
Dann	Benign	0.68

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: rs17637119; hg19: chr3-62435721;