7-95311166-TG-T

Variant names:

• chr7-95311166-TG-T
• rs3917525
• NM_000446.7:c.497+284delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000446.7(PON1):​c.497+284delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6164 hom., cov: 20)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-95311166-TG-T is Benign according to our data. Variant chr7-95311166-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1239123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.497+284delC		intron_variant	Intron 5 of 8	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.497+284delC		intron_variant	Intron 5 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*222+284delC		intron_variant	Intron 5 of 8	3		ENSP00000407359.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42077 AN: 151856 Hom.: 6142 Cov.: 20

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.277 AC: 42135 AN: 151974 Hom.: 6164 Cov.: 20 AF XY: 0.279 AC XY: 20690 AN XY: 74286

African (AFR) AF: 0.364 AC: 15084 AN: 41418

American (AMR) AF: 0.268 AC: 4091 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3468

East Asian (EAS) AF: 0.505 AC: 2603 AN: 5156

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4814

European-Finnish (FIN) AF: 0.219 AC: 2311 AN: 10548

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14953 AN: 67978

Other (OTH) AF: 0.287 AC: 606 AN: 2114

Alfa AF: 0.243 Hom.: 569

Bravo AF: 0.286

Asia WGS AF: 0.406 AC: 1408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3917525; hg19: chr7-94940478;