7-92499847-CAAAA-CAA

Variant names:

• chr7-92499847-CAA-C
• rs5885806
• NM_000466.3:c.2584-11_2584-10delTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:6
• Conservation: PhyloP100: 5.05

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 194603.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}. Variant chr7-92499847-CAA-C is described in Lovd as [Benign]. Variant chr7-92499847-CAA-C is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3	c.2584-11_2584-10delTT		intron_variant	Intron 15 of 23	ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.2584-11_2584-10delTT		intron_variant	Intron 15 of 23	1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 487 AN: 145898 Hom.: 1 Cov.: 0

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

GnomAD3 exomes AF: 0.0769 AC: 11839 AN: 153898 Hom.: 1 AF XY: 0.0807 AC XY: 6564 AN XY: 81294

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 SAS exome AF: 0.110

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.: 10 AF XY: 0.0779 AC XY: 36997 AN XY: 474826

Gnomad4 AFR exome AF: 0.0376

Gnomad4 AMR exome AF: 0.0805

Gnomad4 ASJ exome AF: 0.0777

Gnomad4 EAS exome AF: 0.0503

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0821

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0760

GnomAD4 genome AF: 0.00334 AC: 487 AN: 145992 Hom.: 1 Cov.: 0 AF XY: 0.00312 AC XY: 222 AN XY: 71158

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.000592

Gnomad4 EAS AF: 0.000201

Gnomad4 SAS AF: 0.000429

Gnomad4 FIN AF: 0.00647

Gnomad4 NFE AF: 0.00478

Gnomad4 OTH AF: 0.00247

Alfa AF: 0.134 Hom.: 1774

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:6

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:3

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

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Zellweger spectrum disorders Benign:2

Apr 11, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

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

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

LitVar

Other links and lift over

dbSNP: rs5885806; hg19: chr7-92129161;