rs38809

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000466.3(PEX1):c.358-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,452,726 control chromosomes in the GnomAD database, including 560,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57569 hom., cov: 32)

Exomes 𝑓: 0.88 ( 502642 hom. )

Consequence

PEX1
NM_000466.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.486

Publications

15 publications found

Variant links:

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

PEX1 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 1A (Zellweger)
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, Ambry Genetics
Heimler syndrome 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics
peroxisome biogenesis disorder 1B
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX1 links:

ENSG00000244055 (HGNC:):

ENSG00000244055 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-92518270-C-T is Benign according to our data. Variant chr7-92518270-C-T is described in ClinVar as Benign. ClinVar VariationId is 93112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3 link	c.358-15G>A	intron_variant	Intron 3 of 23	ENST00000248633.9	NP_000457.1	O43933-1
PEX1	NM_001282677.2 link	c.358-15G>A	intron_variant	Intron 3 of 22		NP_001269606.1	O43933A0A0C4DG33
PEX1	NM_001282678.2 link	c.-267-15G>A	intron_variant	Intron 3 of 23		NP_001269607.1	O43933B4DER6
PEX1	XM_047420472.1 link	c.358-15G>A	intron_variant	Intron 3 of 22		XP_047276428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9 link	c.358-15G>A		intron_variant	Intron 3 of 23	1	NM_000466.3	ENSP00000248633.4		O43933-1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132252

AN:

152098

Hom.:

57539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.851

Gnomad AMI

AF:

0.921

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.958

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.871

GnomAD2 exomes

AF:

0.883

AC:

221609

AN:

251108

AF XY:

0.883

show subpopulations

Gnomad AFR exome

AF:

0.845

Gnomad AMR exome

AF:

0.924

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

0.960

Gnomad FIN exome

AF:

0.825

Gnomad NFE exome

AF:

0.869

Gnomad OTH exome

AF:

0.882

GnomAD4 exome

AF:

0.879

AC:

1142857

AN:

1300512

Hom.:

502642

Cov.:

AF XY:

0.879

AC XY:

577003

AN XY:

656152

show subpopulations

African (AFR)

AF:

0.850

AC:

25765

AN:

30326

American (AMR)

AF:

0.921

AC:

41029

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.892

AC:

22449

AN:

25180

East Asian (EAS)

AF:

0.959

AC:

37253

AN:

38860

South Asian (SAS)

AF:

0.900

AC:

74631

AN:

82900

European-Finnish (FIN)

AF:

0.827

AC:

44127

AN:

53330

Middle Eastern (MID)

AF:

0.923

AC:

5006

AN:

5422

European-Non Finnish (NFE)

AF:

0.875

AC:

844015

AN:

964942

Other (OTH)

AF:

0.883

AC:

48582

AN:

55014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

6896

13793

20689

27586

34482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17514

35028

52542

70056

87570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.869

AC:

132335

AN:

152214

Hom.:

57569

Cov.:

AF XY:

0.869

AC XY:

64680

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.851

AC:

35321

AN:

41518

American (AMR)

AF:

0.916

AC:

13996

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.888

AC:

3081

AN:

3470

East Asian (EAS)

AF:

0.957

AC:

4967

AN:

5188

South Asian (SAS)

AF:

0.910

AC:

4389

AN:

4824

European-Finnish (FIN)

AF:

0.829

AC:

8787

AN:

10594

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.865

AC:

58843

AN:

68018

Other (OTH)

AF:

0.872

AC:

1840

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

867

1735

2602

3470

4337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.862

Hom.:

10808

Bravo

AF:

0.877

Asia WGS

AF:

0.902

AC:

3139

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 88% of total chromosomes in ExAC -

Jul 29, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Zellweger spectrum disorders

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder 1A (Zellweger)

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Heimler syndrome 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder 1B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.93

(source)

DANN

Benign

0.56

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over