Variant 7-95302075-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000446.7(PON1):c.909+130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 923,172 control chromosomes in the GnomAD database, including 3,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 667 hom., cov: 21)

Exomes 𝑓: 0.056 ( 2523 hom. )

Consequence

PON1
NM_000446.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 7-95302075-C-T is Benign according to our data. Variant chr7-95302075-C-T is described in ClinVar as [Benign]. Clinvar id is 1228238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.909+130G>A		intron_variant		ENST00000222381.8	NP_000437.3	P27169

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PON1	ENST00000222381.8 linkuse as main transcript	c.909+130G>A	intron_variant	1	NM_000446.7	ENSP00000222381.3	P27169
PON1	ENST00000433729.1 linkuse as main transcript	n.*634+130G>A	intron_variant	3		ENSP00000407359.1	F8WF42
PON1	ENST00000462594.1 linkuse as main transcript	n.199+130G>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

11687

AN:

116622

Hom.:

666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0676

Gnomad EAS

AF:

0.0417

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.164

Gnomad NFE

AF:

0.0614

Gnomad OTH

AF:

0.0832

GnomAD4 exome

AF:

0.0564

AC:

45474

AN:

806522

Hom.:

2523

AF XY:

0.0577

AC XY:

23838

AN XY:

413356

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.0686

Gnomad4 ASJ exome

AF:

0.0662

Gnomad4 EAS exome

AF:

0.0281

Gnomad4 SAS exome

AF:

0.0813

Gnomad4 FIN exome

AF:

0.0696

Gnomad4 NFE exome

AF:

0.0513

Gnomad4 OTH exome

AF:

0.0589

GnomAD4 genome

AF:

0.100

AC:

11702

AN:

116650

Hom.:

667

Cov.:

AF XY:

0.106

AC XY:

5691

AN XY:

53656

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0676

Gnomad4 EAS

AF:

0.0418

Gnomad4 SAS

AF:

0.0992

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.0614

Gnomad4 OTH

AF:

0.0829

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0867

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

DANN

Benign

0.80

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