7-95360361-C-T

Position:

• chr7-95360361-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000940.3(PON3):​c.907-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,118 control chromosomes in the GnomAD database, including 3,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3572 hom., cov: 32)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-95360361-C-T is Benign according to our data. Variant chr7-95360361-C-T is described in ClinVar as [Benign]. Clinvar id is 1249064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3	c.907-230G>A		intron_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.907-230G>A		intron_variant		1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28015 AN: 152000 Hom.: 3570 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.184 AC: 28021 AN: 152118 Hom.: 3572 Cov.: 32 AF XY: 0.190 AC XY: 14156 AN XY: 74360

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.204

Alfa AF: 0.205 Hom.: 3382

Bravo AF: 0.197

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2074352; hg19: chr7-94989673;