rs7786401

Variant names:

• chr7-95404689-G-T
• rs7786401
• ENST00000718462.1:n.589+7661G>T

Variant summary

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

The ENST00000718462.1(ENSG00000233942):​n.589+7661G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,052 control chromosomes in the GnomAD database, including 5,515 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 0.26 (5515 hom., cov: 32)
• Consequence: ENSG00000233942 ENST00000718462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 8 publications found

Genes affected

ENSG00000233942 (HGNC:):

PON2 (HGNC:9205): (paraoxonase 2) This gene encodes a member of the paraoxonase gene family, which includes three known members located adjacent to each other on the long arm of chromosome 7. The encoded protein is ubiquitously expressed in human tissues, membrane-bound, and may act as a cellular antioxidant, protecting cells from oxidative stress. Hydrolytic activity against acylhomoserine lactones, important bacterial quorum-sensing mediators, suggests the encoded protein may also play a role in defense responses to pathogenic bacteria. Mutations in this gene may be associated with vascular disease and a number of quantitative phenotypes related to diabetes. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PON2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.*641C>A		downstream_gene_variant		ENST00000222572.8	NP_000296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.*641C>A		downstream_gene_variant		1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39334 AN: 151934 Hom.: 5503 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.259 AC: 39371 AN: 152052 Hom.: 5515 Cov.: 32 AF XY: 0.268 AC XY: 19945 AN XY: 74318

African (AFR) AF: 0.254 AC: 10526 AN: 41464

American (AMR) AF: 0.216 AC: 3307 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3468

East Asian (EAS) AF: 0.192 AC: 993 AN: 5176

South Asian (SAS) AF: 0.364 AC: 1754 AN: 4824

European-Finnish (FIN) AF: 0.452 AC: 4760 AN: 10540

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16492 AN: 67988

Other (OTH) AF: 0.234 AC: 494 AN: 2108

Alfa AF: 0.232 Hom.: 5677

Bravo AF: 0.236

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		0.044

Splicing

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

Other links and lift over

dbSNP: rs7786401; hg19: chr7-95034001;