NM_003716.4:c.889-4451T>C

Variant names:

• chr3-62666845-A-G
• rs1512015
• NM_003716.4:c.889-4451T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003716.4(CADPS):​c.889-4451T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,984 control chromosomes in the GnomAD database, including 8,450 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 0.32 (8450 hom., cov: 31)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS	NM_003716.4	c.889-4451T>C		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.889-4451T>C		intron_variant	Intron 3 of 29	1	NM_003716.4	ENSP00000373215.4

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48306 AN: 151866 Hom.: 8440 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.318 AC: 48340 AN: 151984 Hom.: 8450 Cov.: 31 AF XY: 0.326 AC XY: 24211 AN XY: 74308

African (AFR) AF: 0.271 AC: 11239 AN: 41450

American (AMR) AF: 0.378 AC: 5773 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3705 AN: 5138

South Asian (SAS) AF: 0.572 AC: 2744 AN: 4794

European-Finnish (FIN) AF: 0.320 AC: 3377 AN: 10566

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19313 AN: 67984

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.328 Hom.: 3050

Bravo AF: 0.321

Asia WGS AF: 0.609 AC: 2112 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-1.2
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: rs1512015; hg19: chr3-62652520;