chr7-95315611-C-T

Position:

• chr7-95315611-C-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.202-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,019,712 control chromosomes in the GnomAD database, including 56,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7020 hom., cov: 32)
  • Exomes 𝑓: 0.32 (49175 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15

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=-0.83).
• BP6: Variant 7-95315611-C-T is Benign according to our data. Variant chr7-95315611-C-T is described in ClinVar as [Benign]. Clinvar id is 1242106.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.202-121G>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.202-121G>A		intron_variant		1	NM_000446.7	ENSP00000222381	P1
PON1	ENST00000433729.1	c.202-162G>A		intron_variant, NMD_transcript_variant		3		ENSP00000407359
PON1	ENST00000470502.1	n.322-121G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43659 AN: 151936 Hom.: 7017 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.323 AC: 280538 AN: 867658 Hom.: 49175 AF XY: 0.321 AC XY: 144504 AN XY: 449906

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.0615

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.287 AC: 43671 AN: 152054 Hom.: 7020 Cov.: 32 AF XY: 0.284 AC XY: 21077 AN XY: 74330

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.0358

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.316

Alfa AF: 0.343 Hom.: 8982

Bravo AF: 0.277

Asia WGS AF: 0.118 AC: 415 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	-0.83
CADD	Benign	8.8
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs854556; hg19: chr7-94944923; COSMIC: COSV55931023;