3-62745917-T-C

Variant names:

• chr3-62745917-T-C
• rs523320
• NM_003716.4:c.888+7524A>G

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+7524A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,228 control chromosomes in the GnomAD database, including 52,729 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 0.83 (52729 hom., cov: 33)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS	NM_003716.4	c.888+7524A>G		intron_variant	Intron 3 of 29	ENST00000383710.9	NP_003707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9	c.888+7524A>G		intron_variant	Intron 3 of 29	1	NM_003716.4	ENSP00000373215.4

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126095 AN: 152110 Hom.: 52688 Cov.: 33

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.829 AC: 126190 AN: 152228 Hom.: 52729 Cov.: 33 AF XY: 0.822 AC XY: 61217 AN XY: 74440

African (AFR) AF: 0.918 AC: 38156 AN: 41552

American (AMR) AF: 0.714 AC: 10915 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3050 AN: 3468

East Asian (EAS) AF: 0.921 AC: 4767 AN: 5176

South Asian (SAS) AF: 0.806 AC: 3888 AN: 4822

European-Finnish (FIN) AF: 0.680 AC: 7192 AN: 10584

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55452 AN: 68014

Other (OTH) AF: 0.842 AC: 1779 AN: 2114

Alfa AF: 0.816 Hom.: 87564

Bravo AF: 0.832

Asia WGS AF: 0.867 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.89
DANN	Benign	0.39
PhyloP100		-1.8
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: rs523320; hg19: chr3-62731592;