rs2659470

Variant names:

• chr3-62625707-C-T
• rs2659470
• NM_003716.4:c.1325+20015G>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.1325+20015G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 150,528 control chromosomes in the GnomAD database, including 66,357 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 0.93 (66351 hom., cov: 32)
  • Exomes 𝑓: 1.0 (6 hom.)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS	NM_003716.4	c.1325+20015G>A		intron_variant	Intron 6 of 29	ENST00000383710.9	NP_003707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9	c.1325+20015G>A		intron_variant	Intron 6 of 29	1	NM_003716.4	ENSP00000373215.4

Frequencies

GnomAD3 genomes AF: 0.934 AC: 140495 AN: 150400 Hom.: 66310 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.940

GnomAD4 exome AF: 1.00 AC: 12 AN: 12 Hom.: 6 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 12 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.934 AC: 140590 AN: 150516 Hom.: 66351 Cov.: 32 AF XY: 0.936 AC XY: 68876 AN XY: 73604

African (AFR) AF: 0.841 AC: 33587 AN: 39928

American (AMR) AF: 0.967 AC: 14754 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 3399 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5168

South Asian (SAS) AF: 0.962 AC: 4636 AN: 4820

European-Finnish (FIN) AF: 0.968 AC: 10265 AN: 10604

Middle Eastern (MID) AF: 0.993 AC: 288 AN: 290

European-Non Finnish (NFE) AF: 0.966 AC: 65659 AN: 67976

Other (OTH) AF: 0.940 AC: 1971 AN: 2096

Alfa AF: 0.956 Hom.: 31555

Asia WGS AF: 0.959 AC: 3336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.57
PhyloP100		0.038
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: rs2659470; hg19: chr3-62611382;