rs854559

chr7-95316560-G-Achr7-95316560-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000446.7(PON1):c.201+174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,030 control chromosomes in the GnomAD database, including 7,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (7017 hom., cov: 33)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.809

Genes affected

PON1 (HGNC:9204): (paraoxonase 1) This gene encodes a member of the paraoxonase family of enzymes and exhibits lactonase and ester hydrolase activity. Following synthesis in the kidney and liver, the enzyme is secreted into the circulation, where it binds to high density lipoprotein (HDL) particles and hydrolyzes thiolactones and xenobiotics, including paraoxon, a metabolite of the insecticide parathion. Polymorphisms in this gene may be associated with coronary artery disease and diabetic retinopathy. The gene is found in a cluster of three related paraoxonase genes on chromosome 7. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-95316560-G-A is Benign according to our data. Variant chr7-95316560-G-A is described in ClinVar as [Benign]. Clinvar id is 1230450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.201+174C>T		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.201+174C>T		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.201+174C>T		intron_variant, NMD_transcript_variant		3
PON1	ENST00000470502.1	n.321+174C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43641 AN: 151912 Hom.: 7015 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.287 AC: 43652 AN: 152030 Hom.: 7017 Cov.: 33 AF XY: 0.284 AC XY: 21082 AN XY: 74296

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.315

Alfa AF: 0.343 Hom.: 8974

Bravo AF: 0.277

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.20
Dann	Benign	0.62

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: rs854559; hg19: chr7-94945872;