rs38809

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 93112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92518270-C-T is described in Lovd as [Benign].

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	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX1	ENST00000248633.9 link	c.358-15G>A	intron_variant	Intron 3 of 23	1	NM_000466.3	ENSP00000248633.4	O43933-1
PEX1	ENST00000428214.5 link	c.358-15G>A	intron_variant	Intron 3 of 22	1		ENSP00000394413.1	A0A0C4DG33
PEX1	ENST00000438045.5 link	c.273+3832G>A	intron_variant	Intron 2 of 20	2		ENSP00000410438.1	O43933-2
PEX1	ENST00000484913.5 link	n.397-15G>A	intron_variant	Intron 3 of 23	2

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

GnomAD3 exomes

AF:

0.883

AC:

221609

AN:

251108

Hom.:

97999

AF XY:

0.883

AC XY:

119821

AN XY:

135738

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 SAS exome

AF:

0.898

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

Gnomad4 AFR exome

AF:

0.850

Gnomad4 AMR exome

AF:

0.921

Gnomad4 ASJ exome

AF:

0.892

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.900

Gnomad4 FIN exome

AF:

0.827

Gnomad4 NFE exome

AF:

0.875

Gnomad4 OTH exome

AF:

0.883

GnomAD4 genome

AF:

0.869

AC:

132335

AN:

152214

Hom.:

57569

Cov.:

AF XY:

0.869

AC XY:

64680

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.851

Gnomad4 AMR

AF:

0.916

Gnomad4 ASJ

AF:

0.888

Gnomad4 EAS

AF:

0.957

Gnomad4 SAS

AF:

0.910

Gnomad4 FIN

AF:

0.829

Gnomad4 NFE

AF:

0.865

Gnomad4 OTH

AF:

0.872

Alfa

AF:

0.862

Hom.:

10515

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 29, 2013

Eurofins Ntd Llc (ga)

Significance: 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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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 -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 07, 2018

GeneDx

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

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

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

DANN

Benign

0.56

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over