7-95308475-CGTGTGT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000446.7(PON1):c.498-270_498-265del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1142 hom., cov: 0)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 7-95308475-CGTGTGT-C is Benign according to our data. Variant chr7-95308475-CGTGTGT-C is described in ClinVar as [Benign]. Clinvar id is 1273749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.498-270_498-265del		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.498-270_498-265del		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*223-270_*223-265del		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 18537 AN: 146964 Hom.: 1141 Cov.: 0

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.126 AC: 18559 AN: 147072 Hom.: 1142 Cov.: 0 AF XY: 0.128 AC XY: 9141 AN XY: 71512

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0861

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.114

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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10548570; hg19: chr7-94937787;