chr7-95305143-G-A

Variant names:

• chr7-95305143-G-A
• rs3917551
• NM_000446.7:c.780+1142C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000446.7(PON1):​c.780+1142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,186 control chromosomes in the GnomAD database, including 832 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 0.091 (832 hom., cov: 32)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 6 publications found

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]

PON1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000446.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON1	NM_000446.7	MANE Select	c.780+1142C>T		intron	N/A	NP_000437.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON1	ENST00000222381.8	TSL:1 MANE Select	c.780+1142C>T		intron	N/A	ENSP00000222381.3
	PON1	ENST00000893040.1		c.771+1142C>T		intron	N/A	ENSP00000563099.1
	PON1	ENST00000893036.1		c.780+1142C>T		intron	N/A	ENSP00000563095.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13777 AN: 152070 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0907 AC: 13797 AN: 152186 Hom.: 832 Cov.: 32 AF XY: 0.0909 AC XY: 6763 AN XY: 74386

African (AFR) AF: 0.150 AC: 6225 AN: 41520

American (AMR) AF: 0.124 AC: 1901 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.119 AC: 616 AN: 5180

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4826

European-Finnish (FIN) AF: 0.0691 AC: 731 AN: 10572

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0520 AC: 3535 AN: 68006

Other (OTH) AF: 0.0804 AC: 170 AN: 2114

Alfa AF: 0.0731 Hom.: 761

Bravo AF: 0.0995

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.71
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3917551; hg19: chr7-94934455;