chr3-62429992-T-A

Variant names:

• chr3-62429992-T-A
• rs4688296
• NM_003716.4:c.3777+8112A>T

Variant summary

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

The NM_003716.4(CADPS):​c.3777+8112A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,986 control chromosomes in the GnomAD database, including 28,678 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 0.61 (28678 hom., cov: 32)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 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.3777+8112A>T		intron	N/A	NP_003707.2
	CADPS	NM_001438347.1		c.3837+8112A>T		intron	N/A	NP_001425276.1
	CADPS	NM_001438348.1		c.3825+8112A>T		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.3777+8112A>T		intron	N/A	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.3750+8112A>T		intron	N/A	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.3660+8112A>T		intron	N/A	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92413 AN: 151868 Hom.: 28628 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.609 AC: 92523 AN: 151986 Hom.: 28678 Cov.: 32 AF XY: 0.608 AC XY: 45147 AN XY: 74304

African (AFR) AF: 0.656 AC: 27196 AN: 41468

American (AMR) AF: 0.680 AC: 10390 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2557 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4397 AN: 5158

South Asian (SAS) AF: 0.584 AC: 2812 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5237 AN: 10570

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37954 AN: 67914

Other (OTH) AF: 0.644 AC: 1360 AN: 2112

Alfa AF: 0.568 Hom.: 3153

Bravo AF: 0.629

Asia WGS AF: 0.683 AC: 2373 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.17
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: rs4688296; hg19: chr3-62415667;