chr3-62673983-T-C

Variant names:

• chr3-62673983-T-C
• rs1858385
• NM_003716.4:c.889-11589A>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.889-11589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,192 control chromosomes in the GnomAD database, including 1,842 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 0.13 (1842 hom., cov: 33)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918
• Publications: 5 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 = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS	NM_003716.4	c.889-11589A>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.889-11589A>G		intron_variant	Intron 3 of 29	1	NM_003716.4	ENSP00000373215.4

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20298 AN: 152074 Hom.: 1834 Cov.: 33

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0697

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.134 AC: 20322 AN: 152192 Hom.: 1842 Cov.: 33 AF XY: 0.138 AC XY: 10247 AN XY: 74390

African (AFR) AF: 0.0375 AC: 1561 AN: 41574

American (AMR) AF: 0.219 AC: 3347 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.00637 AC: 33 AN: 5182

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3207 AN: 10570

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11091 AN: 67982

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.148 Hom.: 5541

Bravo AF: 0.124

Asia WGS AF: 0.0410 AC: 141 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.92
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: rs1858385; hg19: chr3-62659658;