rs854553

Variant names:

• chr7-95299434-A-G
• rs854553
• NM_000446.7:c.910-332T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-95299434-A-G
• chr7-95299434-A-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.910-332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,854 control chromosomes in the GnomAD database, including 33,557 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 0.65 (33557 hom., cov: 30)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.910-332T>C		intron_variant	Intron 8 of 8	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.910-332T>C		intron_variant	Intron 8 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*635-332T>C		intron_variant	Intron 8 of 8	3		ENSP00000407359.1
PON1	ENST00000462594.1	n.200-332T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99043 AN: 151734 Hom.: 33559 Cov.: 30

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.652 AC: 99074 AN: 151854 Hom.: 33557 Cov.: 30 AF XY: 0.654 AC XY: 48484 AN XY: 74186

African (AFR) AF: 0.459 AC: 19015 AN: 41388

American (AMR) AF: 0.695 AC: 10594 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2725 AN: 3470

East Asian (EAS) AF: 0.765 AC: 3919 AN: 5120

South Asian (SAS) AF: 0.769 AC: 3689 AN: 4796

European-Finnish (FIN) AF: 0.635 AC: 6687 AN: 10528

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50131 AN: 67982

Other (OTH) AF: 0.698 AC: 1475 AN: 2112

Alfa AF: 0.716 Hom.: 49749

Bravo AF: 0.646

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.12
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: rs854553; hg19: chr7-94928746;