chr3-62675838-T-C

Variant names:

• chr3-62675838-T-C
• rs17356252
• NM_003716.4:c.889-13444A>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.889-13444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,074 control chromosomes in the GnomAD database, including 3,612 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 0.21 (3612 hom., cov: 32)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 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.889-13444A>G		intron	N/A	NP_003707.2
	CADPS	NM_001438347.1		c.889-13444A>G		intron	N/A	NP_001425276.1
	CADPS	NM_001438348.1		c.889-13444A>G		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.889-13444A>G		intron	N/A	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.889-13444A>G		intron	N/A	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.889-13444A>G		intron	N/A	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32022 AN: 151956 Hom.: 3606 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0777

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.211 AC: 32050 AN: 152074 Hom.: 3612 Cov.: 32 AF XY: 0.216 AC XY: 16023 AN XY: 74314

African (AFR) AF: 0.187 AC: 7745 AN: 41510

American (AMR) AF: 0.278 AC: 4237 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3470

East Asian (EAS) AF: 0.0777 AC: 401 AN: 5164

South Asian (SAS) AF: 0.172 AC: 827 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3687 AN: 10568

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14183 AN: 67968

Other (OTH) AF: 0.175 AC: 369 AN: 2114

Alfa AF: 0.205 Hom.: 2033

Bravo AF: 0.206

Asia WGS AF: 0.132 AC: 459 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		1.7
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: rs17356252; hg19: chr3-62661513;