7-95318697-G-A

Position:

• chr7-95318697-G-A

Variant summary

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

The ENST00000222381.8(PON1):​c.75-304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 310,866 control chromosomes in the GnomAD database, including 15,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6852 hom., cov: 32)
  • Exomes 𝑓: 0.31 (8237 hom.)
• Consequence: PON1 ENST00000222381.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-95318697-G-A is Benign according to our data. Variant chr7-95318697-G-A is described in ClinVar as [Benign]. Clinvar id is 1283941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.75-304C>T		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.75-304C>T		intron_variant		1	NM_000446.7	ENSP00000222381	P1
PON1	ENST00000433729.1	c.75-304C>T		intron_variant, NMD_transcript_variant		3		ENSP00000407359

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42593 AN: 151972 Hom.: 6851 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.307 AC: 48779 AN: 158776 Hom.: 8237 AF XY: 0.299 AC XY: 25247 AN XY: 84436

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.0477

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.280 AC: 42592 AN: 152090 Hom.: 6852 Cov.: 32 AF XY: 0.277 AC XY: 20553 AN XY: 74326

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.313

Alfa AF: 0.351 Hom.: 8851

Bravo AF: 0.269

Asia WGS AF: 0.119 AC: 416 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	-0.87
CADD	Benign	0.11
DANN	Benign	0.33

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: rs854563; hg19: chr7-94948009;