chr3-62492519-C-T

Position:

• chr3-62492519-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADPS	NM_003716.4	c.2728-73G>A		intron_variant		ENST00000383710.9	NP_003707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9	c.2728-73G>A		intron_variant		1	NM_003716.4	ENSP00000373215	P2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19789 AN: 152012 Hom.: 1527 Cov.: 32

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.0737

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.0764

Gnomad4 FIN exome AF: 0.0685

Gnomad4 NFE exome AF: 0.0969

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.130 AC: 19833 AN: 152130 Hom.: 1537 Cov.: 32 AF XY: 0.130 AC XY: 9643 AN XY: 74382

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.0631

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.119

Alfa AF: 0.106 Hom.: 1637

Bravo AF: 0.146

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
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: rs13325751; hg19: chr3-62478194; COSMIC: COSV51872001; COSMIC: COSV51872001;