rs3917548

chr7-95306593-A-G

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.699-227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,212 control chromosomes in the GnomAD database, including 983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.097 (983 hom., cov: 32)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454

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=-0.88).
• BP6: Variant 7-95306593-A-G is Benign according to our data. Variant chr7-95306593-A-G is described in ClinVar as [Benign]. Clinvar id is 1260730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.699-227T>C		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.699-227T>C		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*424-227T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14703 AN: 152094 Hom.: 977 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0968 AC: 14733 AN: 152212 Hom.: 983 Cov.: 32 AF XY: 0.0974 AC XY: 7247 AN XY: 74434

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.0687

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0648 Hom.: 567

Bravo AF: 0.107

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.7
Dann	Benign	0.61

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: rs3917548; hg19: chr7-94935905;