rs3917515

Positions:

• chr7-95312771-G-A
• chr7-95312771-G-C

Variant summary

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

The NM_000446.7(PON1):​c.371-1194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 151,642 control chromosomes in the GnomAD database, including 747 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 0.087 (747 hom., cov: 32)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.371-1194C>T		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.371-1194C>T		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*96-1194C>T		intron_variant, NMD_transcript_variant		3
PON1	ENST00000470502.1	n.491-1194C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13177 AN: 151524 Hom.: 744 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0786

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

GnomAD4 genome AF: 0.0870 AC: 13195 AN: 151642 Hom.: 747 Cov.: 32 AF XY: 0.0873 AC XY: 6472 AN XY: 74136

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0708

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0778

Alfa AF: 0.0254 Hom.: 17

Bravo AF: 0.0968

Asia WGS AF: 0.0940 AC: 328 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.42

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: rs3917515; hg19: chr7-94942083;