rs2012700

Positions:

• chr6-136858249-G-A
• chr6-136858249-G-C
• chr6-136858249-G-T

Variant summary

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

The NM_000288.4(PEX7):​c.527-8378G>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 152,068 control chromosomes in the GnomAD database, including 31,288 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 (31288 hom., cov: 33)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558

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=-0.98).
• 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	UniProt
PEX7	NM_000288.4	c.527-8378G>A		intron_variant		ENST00000318471.5
PEX7	NM_001410945.1	c.413-8378G>A		intron_variant
PEX7	XM_006715502.3	c.340-11641G>A		intron_variant
PEX7	XM_047418874.1	c.526+12068G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX7	ENST00000318471.5	c.527-8378G>A		intron_variant		1	NM_000288.4	P1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97254 AN: 151950 Hom.: 31260 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.626

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: 97340 AN: 152068 Hom.: 31288 Cov.: 33 AF XY: 0.637 AC XY: 47328 AN XY: 74336

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.632

Alfa AF: 0.627 Hom.: 61549

Bravo AF: 0.642

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	-0.98
CADD	Benign	4.5
DANN	Benign	0.29

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: rs2012700; hg19: chr6-137179387;