7-95311726-G-T

Position:

• chr7-95311726-G-T

Variant summary

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

The NM_000446.7(PON1):​c.371-149C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 854,286 control chromosomes in the GnomAD database, including 58,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15768 hom., cov: 32)
  • Exomes 𝑓: 0.32 (42326 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.142

Genes affected

PON1 (HGNC:9204): (paraoxonase 1) This gene encodes a member of the paraoxonase family of enzymes and exhibits lactonase and ester hydrolase activity. Following synthesis in the kidney and liver, the enzyme is secreted into the circulation, where it binds to high density lipoprotein (HDL) particles and hydrolyzes thiolactones and xenobiotics, including paraoxon, a metabolite of the insecticide parathion. Polymorphisms in this gene may be associated with coronary artery disease and diabetic retinopathy. The gene is found in a cluster of three related paraoxonase genes on chromosome 7. [provided by RefSeq, Aug 2017]

PON1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-95311726-G-T is Benign according to our data. Variant chr7-95311726-G-T is described in ClinVar as [Benign]. Clinvar id is 1260271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.371-149C>A		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.371-149C>A		intron_variant		1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*96-149C>A		intron_variant		3		ENSP00000407359.1
PON1	ENST00000470502.1	n.491-149C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63914 AN: 151902 Hom.: 15723 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.324 AC: 227757 AN: 702266 Hom.: 42326 AF XY: 0.323 AC XY: 118355 AN XY: 366612

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.421 AC: 64020 AN: 152020 Hom.: 15768 Cov.: 32 AF XY: 0.422 AC XY: 31336 AN XY: 74292

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.404

Alfa AF: 0.318 Hom.: 7740

Bravo AF: 0.445

Asia WGS AF: 0.544 AC: 1891 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	-0.59
CADD	Benign	15
DANN	Benign	0.58

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: rs1157745; hg19: chr7-94941038;