rs468

Variant names:

• chr7-95368641-A-G
• rs468
• NM_000940.3:c.368-1153T>C

Variant summary

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

The NM_000940.3(PON3):​c.368-1153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 152,158 control chromosomes in the GnomAD database, including 330 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 0.053 (330 hom., cov: 32)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 -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 = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3	c.368-1153T>C		intron_variant	Intron 4 of 8	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.368-1153T>C		intron_variant	Intron 4 of 8	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8139 AN: 152040 Hom.: 330 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0446

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

GnomAD4 genome AF: 0.0535 AC: 8138 AN: 152158 Hom.: 330 Cov.: 32 AF XY: 0.0536 AC XY: 3987 AN XY: 74378

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.0291

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0632

Gnomad4 OTH AF: 0.0446

Alfa AF: 0.0585 Hom.: 292

Bravo AF: 0.0513

Asia WGS AF: 0.119 AC: 414 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	5.9
DANN	Benign	0.49

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: rs468; hg19: chr7-94997953;