7-95363596-G-A

Position:

• chr7-95363596-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000265627.10(PON3):​c.695+267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 487,068 control chromosomes in the GnomAD database, including 58,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15798 hom., cov: 32)
  • Exomes 𝑓: 0.49 (42928 hom.)
• Consequence: PON3 ENST00000265627.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.648

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-95363596-G-A is Benign according to our data. Variant chr7-95363596-G-A is described in ClinVar as [Benign]. Clinvar id is 1239780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3	c.695+267C>T		intron_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.695+267C>T		intron_variant		1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66920 AN: 151544 Hom.: 15791 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.494 AC: 165578 AN: 335410 Hom.: 42928 Cov.: 2 AF XY: 0.501 AC XY: 89715 AN XY: 179100

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.766

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.441 AC: 66948 AN: 151658 Hom.: 15798 Cov.: 32 AF XY: 0.456 AC XY: 33819 AN XY: 74138

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.440

Alfa AF: 0.450 Hom.: 14880

Bravo AF: 0.430

Asia WGS AF: 0.649 AC: 2255 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.87
CADD	Benign	8.3
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs2074353; hg19: chr7-94992908;