NM_000288.4:c.527-3692G>A

Variant names:

• chr6-136862935-G-A
• rs3799476
• NM_000288.4:c.527-3692G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000288.4(PEX7):​c.527-3692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,904 control chromosomes in the GnomAD database, including 31,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31273 hom., cov: 31)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 4 publications found

Genes affected

PEX7 (HGNC:8860): (peroxisomal biogenesis factor 7) This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD). [provided by RefSeq, Oct 2008]

PEX7 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 9B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• rhizomelic chondrodysplasia punctata type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• adult Refsum disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX7	NM_000288.4	c.527-3692G>A		intron_variant	Intron 5 of 9	ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.413-3692G>A		intron_variant	Intron 5 of 9		NP_001397874.1
PEX7	XM_006715502.3	c.340-6955G>A		intron_variant	Intron 3 of 6		XP_006715565.1
PEX7	XM_047418874.1	c.526+16754G>A		intron_variant	Intron 5 of 5		XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.527-3692G>A		intron_variant	Intron 5 of 9	1	NM_000288.4	ENSP00000315680.3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97187 AN: 151786 Hom.: 31245 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.640 AC: 97272 AN: 151904 Hom.: 31273 Cov.: 31 AF XY: 0.637 AC XY: 47301 AN XY: 74228

African (AFR) AF: 0.697 AC: 28861 AN: 41412

American (AMR) AF: 0.635 AC: 9688 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2748 AN: 5142

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4820

European-Finnish (FIN) AF: 0.587 AC: 6177 AN: 10526

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.626 AC: 42581 AN: 67972

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.629 Hom.: 8399

Bravo AF: 0.643

Asia WGS AF: 0.632 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3799476; hg19: chr6-137184073;