rs2614

Positions:

• chr3-157443210-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002852.4(PTX3):​c.*231C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 458,640 control chromosomes in the GnomAD database, including 330 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 0.031 (276 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (54 hom.)
• Consequence: PTX3 NM_002852.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

PTX3 (HGNC:9692): (pentraxin 3) This gene encodes a member of the pentraxin protein family. The expression of this protein is induced by inflammatory cytokines in response to inflammatory stimuli in several mesenchymal and epithelial cell types, particularly endothelial cells and mononuclear phagocytes. The protein promotes fibrocyte differentiation and is involved in regulating inflammation and complement activation. It also plays a role in angiogenesis and tissue remodeling. The protein serves as a biomarker for several inflammatory conditions. [provided by RefSeq, Jun 2016]

VEPH1 (HGNC:25735): (ventricular zone expressed PH domain containing 1) Predicted to enable phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of SMAD protein signal transduction and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTX3	NM_002852.4	c.*231C>T		3_prime_UTR_variant	3/3	ENST00000295927.4	NP_002843.2
VEPH1	NM_001167912.2	c.530-14722G>A		intron_variant		ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTX3	ENST00000295927.4	c.*231C>T		3_prime_UTR_variant	3/3	1	NM_002852.4	ENSP00000295927	P1
VEPH1	ENST00000362010.7	c.530-14722G>A		intron_variant		1	NM_001167912.2	ENSP00000354919	P1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4686 AN: 152162 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00910

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00543 AC: 1663 AN: 306360 Hom.: 54 Cov.: 4 AF XY: 0.00488 AC XY: 766 AN XY: 157064

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00705

Gnomad4 ASJ exome AF: 0.000389

Gnomad4 EAS exome AF: 0.0119

Gnomad4 SAS exome AF: 0.000221

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000374

Gnomad4 OTH exome AF: 0.00870

GnomAD4 genome AF: 0.0308 AC: 4692 AN: 152280 Hom.: 276 Cov.: 32 AF XY: 0.0298 AC XY: 2219 AN XY: 74462

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0185 Hom.: 24

Bravo AF: 0.0346

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.86

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: rs2614; hg19: chr3-157160999;