chr7-95374855-A-G

Position:

• chr7-95374855-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000940.3(PON3):​c.202-2517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,690 control chromosomes in the GnomAD database, including 22,800 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22800 hom., cov: 31)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3	c.202-2517T>C		intron_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.202-2517T>C		intron_variant		1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82085 AN: 151572 Hom.: 22745 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.542 AC: 82198 AN: 151690 Hom.: 22800 Cov.: 31 AF XY: 0.556 AC XY: 41202 AN XY: 74124

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.522

Alfa AF: 0.485 Hom.: 37170

Bravo AF: 0.541

Asia WGS AF: 0.738 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.38

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: rs978903; hg19: chr7-95004167;