rs3799479

chr6-136906956-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000288.4(PEX7):c.904-6502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,020 control chromosomes in the GnomAD database, including 31,626 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 0.63 (31626 hom., cov: 32)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX7	NM_000288.4	c.904-6502G>A		intron_variant		ENST00000318471.5
PEX7	NM_001410945.1	c.790-6502G>A		intron_variant
PEX7	XM_006715502.3	c.610-6502G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX7	ENST00000318471.5	c.904-6502G>A		intron_variant		1	NM_000288.4	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96060 AN: 151902 Hom.: 31584 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.633 AC: 96163 AN: 152020 Hom.: 31626 Cov.: 32 AF XY: 0.630 AC XY: 46797 AN XY: 74314

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.622

Alfa AF: 0.581 Hom.: 17584

Bravo AF: 0.640

Asia WGS AF: 0.597 AC: 2074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.41
Dann	Benign	0.62

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: rs3799479; hg19: chr6-137228094;