3-62450046-G-A

Variant names:

• chr3-62450046-G-A
• rs17637119
• NM_003716.4:c.3637-4249C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	NM_003716.4	MANE Select	c.3637-4249C>T		intron	N/A	NP_003707.2
	CADPS	NM_001438347.1		c.3697-4249C>T		intron	N/A	NP_001425276.1
	CADPS	NM_001438348.1		c.3685-4249C>T		intron	N/A	NP_001425277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	ENST00000383710.9	TSL:1 MANE Select	c.3637-4249C>T		intron	N/A	ENSP00000373215.4
	CADPS	ENST00000612439.4	TSL:1	c.3610-4249C>T		intron	N/A	ENSP00000484365.1
	CADPS	ENST00000283269.13	TSL:1	c.3520-4249C>T		intron	N/A	ENSP00000283269.9

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

African (AFR) AF: 0.0245 AC: 1017 AN: 41502

American (AMR) AF: 0.171 AC: 2613 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.0621 AC: 321 AN: 5170

South Asian (SAS) AF: 0.169 AC: 812 AN: 4814

European-Finnish (FIN) AF: 0.183 AC: 1935 AN: 10578

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9147 AN: 67998

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.120 Hom.: 842

Bravo AF: 0.103

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.68
PhyloP100		-1.3
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: rs17637119; hg19: chr3-62435721;