chr3-62492519-C-A

Variant names:

• chr3-62492519-C-A
• rs13325751
• NM_003716.4:c.2728-73G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003716.4(CADPS):​c.2728-73G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: CADPS NM_003716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	NM_003716.4	MANE Select	c.2728-73G>T		intron	N/A	NP_003707.2
	CADPS	NM_001438347.1		c.2788-73G>T		intron	N/A	NP_001425276.1
	CADPS	NM_001438348.1		c.2776-73G>T		intron	N/A	NP_001425277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	ENST00000383710.9	TSL:1 MANE Select	c.2728-73G>T		intron	N/A	ENSP00000373215.4
	CADPS	ENST00000612439.4	TSL:1	c.2848-73G>T		intron	N/A	ENSP00000484365.1
	CADPS	ENST00000283269.13	TSL:1	c.2758-73G>T		intron	N/A	ENSP00000283269.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1275320 Hom.: 0 AF XY: 0.00000157 AC XY: 1 AN XY: 637110

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29300

American (AMR) AF: 0.00 AC: 0 AN: 40652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22592

East Asian (EAS) AF: 0.00 AC: 0 AN: 38512

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 957156

Other (OTH) AF: 0.00 AC: 0 AN: 53552

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.080
DANN	Benign	0.68
PhyloP100		-0.54

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: rs13325751; hg19: chr3-62478194;