rs854555

chr7-95301079-A-Cchr7-95301079-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000446.7(PON1):c.909+1126T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,590 control chromosomes in the GnomAD database, including 23,488 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 0.54 (23488 hom., cov: 30)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.909+1126T>G		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.909+1126T>G		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*634+1126T>G		intron_variant, NMD_transcript_variant		3
PON1	ENST00000462594.1	n.199+1126T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81565 AN: 151472 Hom.: 23493 Cov.: 30

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.538 AC: 81572 AN: 151590 Hom.: 23488 Cov.: 30 AF XY: 0.538 AC XY: 39808 AN XY: 74024

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.559

Alfa AF: 0.625 Hom.: 63267

Bravo AF: 0.524

Asia WGS AF: 0.466 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.43
Dann	Benign	0.79

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: rs854555; hg19: chr7-94930391;