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GeneBe

7-95308106-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_000446.7(PON1):c.603G>A(p.Ala201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,614,086 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

PON1
NM_000446.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.10
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-95308106-C-T is Benign according to our data. Variant chr7-95308106-C-T is described in ClinVar as [Benign]. Clinvar id is 715878.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-6.1 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PON1NM_000446.7 linkuse as main transcriptc.603G>A p.Ala201= synonymous_variant 6/9 ENST00000222381.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PON1ENST00000222381.8 linkuse as main transcriptc.603G>A p.Ala201= synonymous_variant 6/91 NM_000446.7 P1
PON1ENST00000433729.1 linkuse as main transcriptc.*328G>A 3_prime_UTR_variant, NMD_transcript_variant 6/93

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000868
AC:
132
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.000661
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00150
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00111
AC:
278
AN:
251376
Hom.:
0
AF XY:
0.00113
AC XY:
154
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.000970
Gnomad NFE exome
AF:
0.00187
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00158
AC:
2315
AN:
1461830
Hom.:
2
Cov.:
31
AF XY:
0.00157
AC XY:
1144
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000429
Gnomad4 FIN exome
AF:
0.000842
Gnomad4 NFE exome
AF:
0.00187
Gnomad4 OTH exome
AF:
0.00187
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000867
AC:
132
AN:
152256
Hom.:
0
Cov.:
32
AF XY:
0.000820
AC XY:
61
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.000661
Gnomad4 NFE
AF:
0.00150
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00140
Hom.:
0
Bravo
AF:
0.000899
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00169
EpiControl
AF:
0.00225

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
0.16
Dann
Benign
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148452713; hg19: chr7-94937418; API