3-62492519-C-T

Variant names:

• chr3-62492519-C-T
• rs13325751
• NM_003716.4:c.2728-73G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CADPS	NM_003716.4	c.2728-73G>A		intron_variant	Intron 19 of 29	ENST00000383710.9	NP_003707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9	c.2728-73G>A		intron_variant	Intron 19 of 29	1	NM_003716.4	ENSP00000373215.4

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

African (AFR) AF: 0.200 AC: 5865 AN: 29254

American (AMR) AF: 0.289 AC: 11755 AN: 40608

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 1664 AN: 22584

East Asian (EAS) AF: 0.0507 AC: 1953 AN: 38506

South Asian (SAS) AF: 0.0764 AC: 5860 AN: 76654

European-Finnish (FIN) AF: 0.0685 AC: 3537 AN: 51608

Middle Eastern (MID) AF: 0.0859 AC: 449 AN: 5230

European-Non Finnish (NFE) AF: 0.0969 AC: 92698 AN: 956278

Other (OTH) AF: 0.103 AC: 5486 AN: 53510

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

African (AFR) AF: 0.196 AC: 8114 AN: 41472

American (AMR) AF: 0.215 AC: 3291 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3470

East Asian (EAS) AF: 0.0513 AC: 265 AN: 5168

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4820

European-Finnish (FIN) AF: 0.0631 AC: 669 AN: 10604

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6513 AN: 67998

Other (OTH) AF: 0.119 AC: 251 AN: 2108

Alfa AF: 0.110 Hom.: 4250

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
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13325751; hg19: chr3-62478194; COSMIC: COSV51872001; COSMIC: COSV51872001;