rs28699500

chr7-95317594-G-Achr7-95317594-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000446.7(PON1):c.145+729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.46 (4941 hom., cov: 10)
  • Failed GnomAD Quality Control
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.145+729C>T		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.145+729C>T		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.145+729C>T		intron_variant, NMD_transcript_variant		3
PON1	ENST00000470502.1	n.265+729C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 33334 AN: 72096 Hom.: 4938 Cov.: 10 FAILED QC

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.492

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.474

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.462 AC: 33341 AN: 72100 Hom.: 4941 Cov.: 10 AF XY: 0.465 AC XY: 16154 AN XY: 34706

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.477

Alfa AF: 0.199 Hom.: 162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.57
Dann	Benign	0.23

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: rs28699500; hg19: chr7-94946906;