Variant 7-95367601-T-G 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 ENST00000265627.10(PON3):c.368-113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,143,818 control chromosomes in the GnomAD database, including 151,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21846 hom., cov: 32)

Exomes 𝑓: 0.50 ( 129744 hom. )

Consequence

PON3
ENST00000265627.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.504

Variant links:

Genes affected

PON3 (HGNC:9206): (paraoxonase 3) This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with high-density lipoprotein (HDL). The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of low-density lipoprotein (LDL), a function that is believed to slow the initiation and progression of atherosclerosis. Alternatively spliced variants which encode different protein isoforms have been described; however, only one has been fully characterized. [provided by RefSeq, Jul 2008]

PON3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-95367601-T-G is Benign according to our data. Variant chr7-95367601-T-G is described in ClinVar as [Benign]. Clinvar id is 1221645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3 linkuse as main transcript	c.368-113A>C		intron_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10 linkuse as main transcript	c.368-113A>C		intron_variant		1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80472

AN:

151934

Hom.:

21797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.505

GnomAD4 exome

AF:

0.504

AC:

499965

AN:

991766

Hom.:

129744

AF XY:

0.507

AC XY:

259327

AN XY:

511286

show subpopulations

Gnomad4 AFR exome

AF:

0.580

Gnomad4 AMR exome

AF:

0.654

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.630

Gnomad4 FIN exome

AF:

0.591

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.507

GnomAD4 genome

AF:

0.530

AC:

80578

AN:

152052

Hom.:

21846

Cov.:

AF XY:

0.544

AC XY:

40401

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.585

Gnomad4 ASJ

AF:

0.413

Gnomad4 EAS

AF:

0.767

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.469

Hom.:

17078

Bravo

AF:

0.529

Asia WGS

AF:

0.709

AC:

2463

AN:

3478

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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.2

DANN

Benign

0.40

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