7-92499847-CAAA-CAAAA

Position:

• chr7-92499847-CAAA-CAAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000466.3(PEX1):​c.2584-10dupT variant causes a intron change. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (145 hom., cov: 0)
  • Exomes 𝑓: 0.040 (49 hom.)
• Consequence: PEX1 NM_000466.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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]

PEX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-92499847-C-CA is Benign according to our data. Variant chr7-92499847-C-CA is described in ClinVar as [Benign]. Clinvar id is 286353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX1	NM_000466.3	c.2584-10dupT		intron_variant		ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.2584-10dupT		intron_variant		1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 5911 AN: 146112 Hom.: 146 Cov.: 0

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.0124

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0186

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0292

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0339

GnomAD3 exomes AF: 0.0456 AC: 7020 AN: 153898 Hom.: 3 AF XY: 0.0468 AC XY: 3801 AN XY: 81294

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.0120

Gnomad SAS exome AF: 0.0413

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0601

Gnomad OTH exome AF: 0.0398

GnomAD4 exome AF: 0.0397 AC: 46580 AN: 1173076 Hom.: 49 Cov.: 0 AF XY: 0.0394 AC XY: 23233 AN XY: 589258

Gnomad4 AFR exome AF: 0.0515

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.00667

Gnomad4 SAS exome AF: 0.0258

Gnomad4 FIN exome AF: 0.0412

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.0405 AC: 5923 AN: 146208 Hom.: 145 Cov.: 0 AF XY: 0.0401 AC XY: 2862 AN XY: 71286

Gnomad4 AFR AF: 0.0522

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0186

Gnomad4 EAS AF: 0.0107

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.0336

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Zellweger spectrum disorders Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 25, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs5885806; hg19: chr7-92129161;