chr7-95372046-A-T

Position:

• chr7-95372046-A-T

Variant summary

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

The NM_000940.3(PON3):​c.367+127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,060,028 control chromosomes in the GnomAD database, including 466,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68652 hom., cov: 30)
  • Exomes 𝑓: 0.94 (397813 hom.)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780

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=-0.95).
• BP6: Variant 7-95372046-A-T is Benign according to our data. Variant chr7-95372046-A-T is described in ClinVar as [Benign]. Clinvar id is 1294630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON3	NM_000940.3	c.367+127T>A		intron_variant		ENST00000265627.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON3	ENST00000265627.10	c.367+127T>A		intron_variant		1	NM_000940.3	P1

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144263 AN: 151966 Hom.: 68593 Cov.: 30

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.959

GnomAD4 exome AF: 0.936 AC: 849426 AN: 907942 Hom.: 397813 AF XY: 0.936 AC XY: 440217 AN XY: 470280

Gnomad4 AFR exome AF: 0.980

Gnomad4 AMR exome AF: 0.978

Gnomad4 ASJ exome AF: 0.944

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.945

Gnomad4 FIN exome AF: 0.935

Gnomad4 NFE exome AF: 0.936

Gnomad4 OTH exome AF: 0.938

GnomAD4 genome AF: 0.949 AC: 144382 AN: 152086 Hom.: 68652 Cov.: 30 AF XY: 0.949 AC XY: 70559 AN XY: 74338

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.959

Alfa AF: 0.940 Hom.: 8358

Bravo AF: 0.952

Asia WGS AF: 0.879 AC: 3059 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	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.41

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: rs2375002; hg19: chr7-95001358;