7-92499847-CAAAA-CAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_000466.3(PEX1):c.2584-10delT variant causes a intron change. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.75 ( 40360 hom., cov: 0)

Exomes 𝑓: 0.59 ( 117822 hom. )

Failed GnomAD Quality Control

Consequence

PEX1
NM_000466.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:12

Conservation

PhyloP100: 5.05

Publications

6 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 -9 ACMG points.

BP6

Variant 7-92499847-CA-C is Benign according to our data. Variant chr7-92499847-CA-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 360922.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3 link	c.2584-10delT		intron_variant	Intron 15 of 23	ENST00000248633.9	NP_000457.1	O43933-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9 link	c.2584-10delT		intron_variant	Intron 15 of 23	1	NM_000466.3	ENSP00000248633.4		O43933-1

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

108881

AN:

146078

Hom.:

40356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.782

Gnomad MID

AF:

0.776

Gnomad NFE

AF:

0.800

Gnomad OTH

AF:

0.753

GnomAD2 exomes

AF:

0.597

AC:

91804

AN:

153898

AF XY:

0.596

show subpopulations

Gnomad AFR exome

AF:

0.538

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.584

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.585

AC:

683458

AN:

1168006

Hom.:

117822

Cov.:

AF XY:

0.584

AC XY:

342329

AN XY:

586582

show subpopulations

African (AFR)

AF:

0.510

AC:

14125

AN:

27696

American (AMR)

AF:

0.556

AC:

21156

AN:

38068

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

12363

AN:

22122

East Asian (EAS)

AF:

0.547

AC:

18653

AN:

34076

South Asian (SAS)

AF:

0.568

AC:

40829

AN:

71876

European-Finnish (FIN)

AF:

0.583

AC:

25998

AN:

44584

Middle Eastern (MID)

AF:

0.647

AC:

3201

AN:

4950

European-Non Finnish (NFE)

AF:

0.593

AC:

518817

AN:

875486

Other (OTH)

AF:

0.576

AC:

28316

AN:

49148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.597

Heterozygous variant carriers

13691

27382

41073

54764

68455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15760

31520

47280

63040

78800

<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:

0.745

AC:

108923

AN:

146176

Hom.:

40360

Cov.:

AF XY:

0.746

AC XY:

53145

AN XY:

71248

show subpopulations

African (AFR)

AF:

0.624

AC:

24523

AN:

39282

American (AMR)

AF:

0.768

AC:

11319

AN:

14734

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

2635

AN:

3382

East Asian (EAS)

AF:

0.689

AC:

3426

AN:

4970

South Asian (SAS)

AF:

0.851

AC:

3962

AN:

4658

European-Finnish (FIN)

AF:

0.782

AC:

7449

AN:

9528

Middle Eastern (MID)

AF:

0.778

AC:

224

AN:

288

European-Non Finnish (NFE)

AF:

0.800

AC:

53140

AN:

66432

Other (OTH)

AF:

0.754

AC:

1521

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1338

2676

4013

5351

6689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.585

Hom.:

1774

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:12

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 26, 2022

Genetic Services Laboratory, University of Chicago

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:Likely 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: ExAC: 34.4% (31/90) South Asian chromosomes -

Nov 23, 2016

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder 1A (Zellweger)

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Zellweger spectrum disorders

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 15, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:1

Jun 15, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 10, 2019

GeneDx

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

PhyloP100

5.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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