chr7-92499847-CAA-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_000466.3(PEX1):c.2584-11_2584-10delTT variant causes a intron change. The variant allele was found at a frequency of 0.0673 in 1,106,330 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 0)

Exomes 𝑓: 0.077 ( 10 hom. )

Consequence

PEX1
NM_000466.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

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-CAA-C is Benign according to our data. Variant chr7-92499847-CAA-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 194603.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00334 (487/145992) while in subpopulation NFE AF = 0.00478 (317/66316). AF 95% confidence interval is 0.00435. There are 1 homozygotes in GnomAd4. There are 222 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3 link	c.2584-11_2584-10delTT		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.2584-11_2584-10delTT		intron_variant	Intron 15 of 23	1	NM_000466.3	ENSP00000248633.4		O43933-1

Frequencies

GnomAD3 genomes

AF:

0.00334

AC:

487

AN:

145898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.000592

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.000429

Gnomad FIN

AF:

0.00647

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00250

GnomAD2 exomes

AF:

0.0769

AC:

11839

AN:

153898

AF XY:

0.0807

show subpopulations

Gnomad AFR exome

AF:

0.0294

Gnomad AMR exome

AF:

0.0838

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.0565

Gnomad FIN exome

AF:

0.0755

Gnomad NFE exome

AF:

0.0777

Gnomad OTH exome

AF:

0.0917

GnomAD4 exome

AF:

0.0771

AC:

74006

AN:

960338

Hom.:

AF XY:

0.0779

AC XY:

36997

AN XY:

474826

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0376

AC:

965

AN:

25678

American (AMR)

AF:

0.0805

AC:

2494

AN:

30992

Ashkenazi Jewish (ASJ)

AF:

0.0777

AC:

1314

AN:

16910

East Asian (EAS)

AF:

0.0503

AC:

1477

AN:

29376

South Asian (SAS)

AF:

0.103

AC:

5183

AN:

50416

European-Finnish (FIN)

AF:

0.0821

AC:

2898

AN:

35290

Middle Eastern (MID)

AF:

0.0547

AC:

233

AN:

4256

European-Non Finnish (NFE)

AF:

0.0775

AC:

56391

AN:

727292

Other (OTH)

AF:

0.0760

AC:

3051

AN:

40128

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.270

Heterozygous variant carriers

9362

18723

28085

37446

46808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1988

3976

5964

7952

9940

<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:

0.00334

AC:

487

AN:

145992

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

222

AN XY:

71158

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

39296

American (AMR)

AF:

0.00353

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.000592

AC:

AN:

3376

East Asian (EAS)

AF:

0.000201

AC:

AN:

4970

South Asian (SAS)

AF:

0.000429

AC:

AN:

4660

European-Finnish (FIN)

AF:

0.00647

AC:

AN:

9434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00478

AC:

317

AN:

66316

Other (OTH)

AF:

0.00247

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.134

Hom.:

1774

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 16, 2014

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Zellweger spectrum disorders

Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 11, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder 1A (Zellweger)

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.0

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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