chr3-62747691-C-T

Variant names:

• chr3-62747691-C-T
• rs580384
• NM_003716.4:c.888+5750G>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.888+5750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,220 control chromosomes in the GnomAD database, including 59,881 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 0.89 (59881 hom., cov: 32)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003716.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	NM_003716.4	MANE Select	c.888+5750G>A		intron	N/A	NP_003707.2
	CADPS	NM_001438347.1		c.888+5750G>A		intron	N/A	NP_001425276.1
	CADPS	NM_001438348.1		c.888+5750G>A		intron	N/A	NP_001425277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	ENST00000383710.9	TSL:1 MANE Select	c.888+5750G>A		intron	N/A	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.888+5750G>A		intron	N/A	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.888+5750G>A		intron	N/A	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134811 AN: 152102 Hom.: 59842 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.886 AC: 134903 AN: 152220 Hom.: 59881 Cov.: 32 AF XY: 0.881 AC XY: 65563 AN XY: 74392

African (AFR) AF: 0.878 AC: 36441 AN: 41522

American (AMR) AF: 0.827 AC: 12647 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3173 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4724 AN: 5172

South Asian (SAS) AF: 0.807 AC: 3896 AN: 4828

European-Finnish (FIN) AF: 0.841 AC: 8901 AN: 10588

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62138 AN: 68026

Other (OTH) AF: 0.886 AC: 1867 AN: 2108

Alfa AF: 0.901 Hom.: 183225

Bravo AF: 0.883

Asia WGS AF: 0.858 AC: 2980 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.23
PhyloP100		-2.6
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: rs580384; hg19: chr3-62733366;