ENST00000902748.1:c.*2325G>A

Variant names:

• chr7-95357648-C-T
• rs916864
• ENST00000902748.1:c.*2325G>A

Variant summary

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

The ENST00000902748.1(PON3):​c.*2325G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,212 control chromosomes in the GnomAD database, including 3,572 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 0.18 (3572 hom., cov: 32)
• Consequence: PON3 ENST00000902748.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 3 publications found

Genes affected

PON3 (HGNC:9206): (paraoxonase 3) This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with high-density lipoprotein (HDL). The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of low-density lipoprotein (LDL), a function that is believed to slow the initiation and progression of atherosclerosis. Alternatively spliced variants which encode different protein isoforms have been described; however, only one has been fully characterized. [provided by RefSeq, Jul 2008]

PON3 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000902748.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON3	ENST00000902748.1		c.*2325G>A		3_prime_UTR	Exon 10 of 10	ENSP00000572807.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28035 AN: 152094 Hom.: 3570 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.184 AC: 28041 AN: 152212 Hom.: 3572 Cov.: 32 AF XY: 0.190 AC XY: 14170 AN XY: 74430

African (AFR) AF: 0.0652 AC: 2711 AN: 41556

American (AMR) AF: 0.329 AC: 5032 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.591 AC: 3053 AN: 5162

South Asian (SAS) AF: 0.253 AC: 1222 AN: 4824

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13024 AN: 67984

Other (OTH) AF: 0.204 AC: 432 AN: 2116

Alfa AF: 0.202 Hom.: 4336

Bravo AF: 0.197

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.16
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs916864; hg19: chr7-94986960;