rs304172

chr3-62796793-G-Achr3-62796793-G-C

Variant summary

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

The NM_003716.4(CADPS):c.442-30809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,112 control chromosomes in the GnomAD database, including 646 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 0.079 (646 hom., cov: 33)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS	NM_003716.4	c.442-30809C>T		intron_variant		ENST00000383710.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS	ENST00000383710.9	c.442-30809C>T		intron_variant		1	NM_003716.4	P2

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11924 AN: 151992 Hom.: 640 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0393

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0786 AC: 11954 AN: 152112 Hom.: 646 Cov.: 33 AF XY: 0.0791 AC XY: 5880 AN XY: 74352

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0456

Gnomad4 ASJ AF: 0.0393

Gnomad4 EAS AF: 0.0934

Gnomad4 SAS AF: 0.0637

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0568 Hom.: 332

Bravo AF: 0.0836

Asia WGS AF: 0.0900 AC: 313 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.7
Dann	Benign	0.76

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: rs304172; hg19: chr3-62782468;