rs3917478

chr7-95322257-T-C

Variant summary

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

The NM_000446.7(PON1):c.74+2145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 128,478 control chromosomes in the GnomAD database, including 830 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 0.11 (830 hom., cov: 31)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.74+2145A>G		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.74+2145A>G		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.74+2145A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 14756 AN: 128436 Hom.: 830 Cov.: 31

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0751

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0600

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.115 AC: 14760 AN: 128478 Hom.: 830 Cov.: 31 AF XY: 0.116 AC XY: 7122 AN XY: 61610

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.0751

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.107

Alfa AF: 0.109 Hom.: 1304

Bravo AF: 0.0932

Asia WGS AF: 0.148 AC: 514 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.5
Dann	Benign	0.46

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: rs3917478; hg19: chr7-94951569;