rs3917481

chr7-95321453-C-T

Variant summary

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

The NM_000446.7(PON1):c.74+2949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 152,318 control chromosomes in the GnomAD database, including 177 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 0.037 (177 hom., cov: 32)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.74+2949G>A		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.74+2949G>A		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.74+2949G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5674 AN: 152200 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0374 AC: 5691 AN: 152318 Hom.: 177 Cov.: 32 AF XY: 0.0382 AC XY: 2845 AN XY: 74480

Gnomad4 AFR AF: 0.0812

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0168 Hom.: 46

Bravo AF: 0.0392

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.31
Dann	Benign	0.63

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: rs3917481; hg19: chr7-94950765;