Variant 7-95311470-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000446.7(PON1):c.478A>G(p.Arg160Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,614,108 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0029 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 109 hom. )

Consequence

PON1
NM_000446.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Variant links:

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 links:

PON1 (HGNC:):

PON1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031523407).

BP6

Variant 7-95311470-T-C is Benign according to our data. Variant chr7-95311470-T-C is described in ClinVar as [Benign]. Clinvar id is 1251798.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7 linkuse as main transcript	c.478A>G	p.Arg160Gly	missense_variant	5/9	ENST00000222381.8	NP_000437.3	P27169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PON1	ENST00000222381.8 linkuse as main transcript	c.478A>G	p.Arg160Gly	missense_variant	5/9	1	NM_000446.7	ENSP00000222381.3	P27169
PON1	ENST00000433729.1 linkuse as main transcript	n.*203A>G		non_coding_transcript_exon_variant	5/9	3		ENSP00000407359.1	F8WF42
PON1	ENST00000433729.1 linkuse as main transcript	n.*203A>G		3_prime_UTR_variant	5/9	3		ENSP00000407359.1	F8WF42
PON1	ENST00000470502.1 linkuse as main transcript	n.*20A>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

446

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0770

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00598

AC:

1502

AN:

251310

Hom.:

AF XY:

0.00562

AC XY:

764

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0769

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00227

AC:

3325

AN:

1461780

Hom.:

109

Cov.:

AF XY:

0.00228

AC XY:

1659

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0739

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00291

AC:

444

AN:

152328

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

261

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0770

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00267

Hom.:

Bravo

AF:

0.00342

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00596

AC:

724

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

This variant is associated with the following publications: (PMID: 12588779) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.028

Eigen_PC

Benign

0.012

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.090

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.030

Polyphen

0.17

Vest4

0.30

MVP

0.47

MPC

0.21

ClinPred

0.057

GERP RS

3.5

Varity_R

0.74

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over