chr3-62821765-C-T

Position:

• chr3-62821765-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.441+52824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 152,300 control chromosomes in the GnomAD database, including 72,431 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 0.98 (72431 hom., cov: 32)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADPS	NM_003716.4	c.441+52824G>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.441+52824G>A		intron_variant		1	NM_003716.4	ENSP00000373215.4

Frequencies

GnomAD3 genomes AF: 0.975 AC: 148407 AN: 152182 Hom.: 72374 Cov.: 32

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.974

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

GnomAD4 genome AF: 0.975 AC: 148523 AN: 152300 Hom.: 72431 Cov.: 32 AF XY: 0.976 AC XY: 72664 AN XY: 74450

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.974

Alfa AF: 0.958 Hom.: 3229

Bravo AF: 0.978

Asia WGS AF: 0.998 AC: 3468 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.13

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: rs481279; hg19: chr3-62807440;