rs3799476

Positions:

• chr6-136862935-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.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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
PEX7	NM_000288.4	c.527-3692G>A		intron_variant		ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.413-3692G>A		intron_variant			NP_001397874.1
PEX7	XM_006715502.3	c.340-6955G>A		intron_variant			XP_006715565.1
PEX7	XM_047418874.1	c.526+16754G>A		intron_variant			XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.527-3692G>A		intron_variant		1	NM_000288.4	ENSP00000315680	P1

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

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.633

Alfa AF: 0.628 Hom.: 8216

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

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: rs3799476; hg19: chr6-137184073;