7-95308312-G-A

Position:

• chr7-95308312-G-A

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.498-101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,098,950 control chromosomes in the GnomAD database, including 3,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (953 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2790 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.169

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=-0.86).
• BP6: Variant 7-95308312-G-A is Benign according to our data. Variant chr7-95308312-G-A is described in ClinVar as [Benign]. Clinvar id is 1243112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.498-101C>T		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.498-101C>T		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*223-101C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14546 AN: 152072 Hom.: 948 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0855

GnomAD4 exome AF: 0.0672 AC: 63634 AN: 946760 Hom.: 2790 AF XY: 0.0660 AC XY: 32202 AN XY: 488278

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.0684

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0674

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0541

Gnomad4 OTH exome AF: 0.0736

GnomAD4 genome AF: 0.0958 AC: 14574 AN: 152190 Hom.: 953 Cov.: 32 AF XY: 0.0963 AC XY: 7170 AN XY: 74426

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0647 Hom.: 387

Bravo AF: 0.106

Asia WGS AF: 0.101 AC: 353 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 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.71

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: rs3917541; hg19: chr7-94937624;