3-62625568-C-T

Position:

• chr3-62625568-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003716.4(CADPS):​c.1325+20154G>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 150,602 control chromosomes in the GnomAD database, including 66,396 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 (66386 hom., cov: 31)
  • Exomes 𝑓: 0.92 (10 hom.)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• 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/exons	MANE	Protein	UniProt
CADPS	NM_003716.4	c.1325+20154G>A		intron_variant		ENST00000383710.9	NP_003707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9	c.1325+20154G>A		intron_variant		1	NM_003716.4	ENSP00000373215.4

Frequencies

GnomAD3 genomes AF: 0.934 AC: 140564 AN: 150462 Hom.: 66346 Cov.: 31

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: 0.961

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.940

GnomAD4 exome AF: 0.917 AC: 22 AN: 24 Hom.: 10 Cov.: 0 AF XY: 0.909 AC XY: 20 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.950

GnomAD4 genome AF: 0.934 AC: 140657 AN: 150578 Hom.: 66386 Cov.: 31 AF XY: 0.936 AC XY: 68889 AN XY: 73606

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.941

Alfa AF: 0.964 Hom.: 121838

Bravo AF: 0.931

Asia WGS AF: 0.959 AC: 3337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2965051; hg19: chr3-62611243;