7-95301923-T-TAA

Position:

• chr7-95301923-T-TAA

Variant summary

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

The NM_000446.7(PON1):​c.909+281_909+282insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (11657 hom., cov: 0)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.153

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 7-95301923-T-TAA is Benign according to our data. Variant chr7-95301923-T-TAA is described in ClinVar as [Benign]. Clinvar id is 1240752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.909+281_909+282insTT		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.909+281_909+282insTT		intron_variant		1	NM_000446.7	ENSP00000222381	P1
PON1	ENST00000433729.1	c.*634+281_*634+282insTT		intron_variant, NMD_transcript_variant		3		ENSP00000407359
PON1	ENST00000462594.1	n.199+281_199+282insTT		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 55501 AN: 135444 Hom.: 11656 Cov.: 0

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.410 AC: 55511 AN: 135446 Hom.: 11657 Cov.: 0 AF XY: 0.407 AC XY: 26410 AN XY: 64810

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.430

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 20, 2021

- -

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: rs10638749; hg19: chr7-94931235;