7-95297930-T-C

Variant names:

• chr7-95297930-T-C
• rs854550
• NM_000446.7:c.*1014A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000446.7(PON1):​c.*1014A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,210 control chromosomes in the GnomAD database, including 50,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50279 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PON1 NM_000446.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.*1014A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.*1014A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000446.7	ENSP00000222381.3

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123474 AN: 152092 Hom.: 50237 Cov.: 33

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.835

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.812 AC: 123573 AN: 152210 Hom.: 50279 Cov.: 33 AF XY: 0.814 AC XY: 60573 AN XY: 74410

African (AFR) AF: 0.806 AC: 33472 AN: 41542

American (AMR) AF: 0.857 AC: 13121 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2989 AN: 3470

East Asian (EAS) AF: 0.905 AC: 4684 AN: 5178

South Asian (SAS) AF: 0.869 AC: 4196 AN: 4826

European-Finnish (FIN) AF: 0.751 AC: 7946 AN: 10578

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54499 AN: 67996

Other (OTH) AF: 0.829 AC: 1753 AN: 2114

Alfa AF: 0.813 Hom.: 131959

Bravo AF: 0.820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.56
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: rs854550; hg19: chr7-94927242;