chr7-95302632-G-GA

Variant names:

• chr7-95302632-G-GA
• rs142523546
• NM_000446.7:c.781-300dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000446.7(PON1):​c.781-300dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 146,736 control chromosomes in the GnomAD database, including 3,077 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3077 hom., cov: 28)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 7-95302632-G-GA is Benign according to our data. Variant chr7-95302632-G-GA is described in ClinVar as [Benign]. Clinvar id is 1247214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.781-300dupT		intron_variant	Intron 7 of 8	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.781-300_781-299insT		intron_variant	Intron 7 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*506-300_*506-299insT		intron_variant	Intron 7 of 8	3		ENSP00000407359.1
PON1	ENST00000462594.1	n.-230_-229insT		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29352 AN: 146632 Hom.: 3071 Cov.: 28

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.200 AC: 29379 AN: 146736 Hom.: 3077 Cov.: 28 AF XY: 0.202 AC XY: 14394 AN XY: 71300

African (AFR) AF: 0.276 AC: 11075 AN: 40138

American (AMR) AF: 0.191 AC: 2834 AN: 14800

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 654 AN: 3426

East Asian (EAS) AF: 0.438 AC: 2216 AN: 5064

South Asian (SAS) AF: 0.195 AC: 902 AN: 4630

European-Finnish (FIN) AF: 0.137 AC: 1268 AN: 9248

Middle Eastern (MID) AF: 0.122 AC: 35 AN: 288

European-Non Finnish (NFE) AF: 0.150 AC: 9964 AN: 66238

Other (OTH) AF: 0.201 AC: 409 AN: 2034

Alfa AF: 0.0496 Hom.: 48

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061
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: rs142523546; hg19: chr7-94931944;