rs113104510

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.358-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,477,148 control chromosomes in the GnomAD database, including 1,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 155 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1093 hom. )

Consequence

PEX1
NM_000466.3 intron

Scores

Splicing: ADA: 0.00001241

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.378

Publications

2 publications found

Variant links:

COSMIC-nc: COSV104373587

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: Ambry Genetics, Myriad Women’s Health
Heimler syndrome 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: 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=-0.86).

BP6

Variant 7-92518266-C-G is Benign according to our data. Variant chr7-92518266-C-G is described in ClinVar as Benign. ClinVar VariationId is 256221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000466.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX1	NM_000466.3	MANE Select	c.358-11G>C	intron	N/A	NP_000457.1	O43933-1
PEX1	NM_001282677.2		c.358-11G>C	intron	N/A	NP_001269606.1	A0A0C4DG33
PEX1	NM_001282678.2		c.-267-11G>C	intron	N/A	NP_001269607.1	B4DER6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX1	ENST00000248633.9	TSL:1 MANE Select	c.358-11G>C	intron	N/A	ENSP00000248633.4	O43933-1
PEX1	ENST00000428214.5	TSL:1	c.358-11G>C	intron	N/A	ENSP00000394413.1	A0A0C4DG33
PEX1	ENST00000951788.1		c.358-11G>C	intron	N/A	ENSP00000621847.1

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6132

AN:

152008

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00944

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0424

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0311

GnomAD2 exomes

AF:

0.0334

AC:

8393

AN:

251138

AF XY:

0.0334

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.00826

Gnomad FIN exome

AF:

0.0407

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0380

AC:

50393

AN:

1325022

Hom.:

1093

Cov.:

AF XY:

0.0379

AC XY:

25258

AN XY:

666876

show subpopulations

African (AFR)

AF:

0.0528

AC:

1629

AN:

30838

American (AMR)

AF:

0.0149

AC:

664

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

405

AN:

25286

East Asian (EAS)

AF:

0.00521

AC:

203

AN:

38952

South Asian (SAS)

AF:

0.0261

AC:

2181

AN:

83460

European-Finnish (FIN)

AF:

0.0424

AC:

2265

AN:

53358

Middle Eastern (MID)

AF:

0.0241

AC:

132

AN:

5484

European-Non Finnish (NFE)

AF:

0.0415

AC:

41014

AN:

987394

Other (OTH)

AF:

0.0341

AC:

1900

AN:

55688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2488

4977

7465

9954

12442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1384

2768

4152

5536

6920

<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:

0.0404

AC:

6153

AN:

152126

Hom.:

155

Cov.:

AF XY:

0.0403

AC XY:

2996

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0529

AC:

2193

AN:

41494

American (AMR)

AF:

0.0230

AC:

352

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.00985

AC:

AN:

5180

South Asian (SAS)

AF:

0.0261

AC:

126

AN:

4820

European-Finnish (FIN)

AF:

0.0424

AC:

448

AN:

10560

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0417

AC:

2836

AN:

68004

Other (OTH)

AF:

0.0313

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

300

601

901

1202

1502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0401

Hom.:

Bravo

AF:

0.0383

Asia WGS

AF:

0.0380

AC:

130

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Zellweger spectrum disorders (2)

not specified (1)

Peroxisome biogenesis disorder 1A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

(source)

DANN

Benign

0.54

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over