6-136864155-A-G

Variant names:

• chr6-136864155-A-G
• rs1474987
• NM_000288.4:c.527-2472A>G

Variant summary

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

The NM_000288.4(PEX7):​c.527-2472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,772 control chromosomes in the GnomAD database, including 26,841 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 0.59 (26841 hom., cov: 30)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 1 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• rhizomelic chondrodysplasia punctata type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Myriad Women’s Health
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000288.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX7	NM_000288.4	MANE Select	c.527-2472A>G		intron	N/A	NP_000279.1	Q6FGN1
	PEX7	NM_001410945.1		c.413-2472A>G		intron	N/A	NP_001397874.1	A0A7I2V2J8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX7	ENST00000318471.5	TSL:1 MANE Select	c.527-2472A>G		intron	N/A	ENSP00000315680.3	O00628-1
	PEX7	ENST00000678557.1		c.413-2472A>G		intron	N/A	ENSP00000502962.1	A0A7I2V2J8
	PEX7	ENST00000865443.1		c.527-2472A>G		intron	N/A	ENSP00000535502.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90193 AN: 151656 Hom.: 26828 Cov.: 30

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.595 AC: 90247 AN: 151772 Hom.: 26841 Cov.: 30 AF XY: 0.593 AC XY: 43963 AN XY: 74144

African (AFR) AF: 0.612 AC: 25303 AN: 41346

American (AMR) AF: 0.592 AC: 9027 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2116 AN: 3464

East Asian (EAS) AF: 0.531 AC: 2743 AN: 5168

South Asian (SAS) AF: 0.622 AC: 2998 AN: 4818

European-Finnish (FIN) AF: 0.573 AC: 6016 AN: 10494

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40220 AN: 67926

Other (OTH) AF: 0.584 AC: 1231 AN: 2108

Alfa AF: 0.590 Hom.: 4411

Bravo AF: 0.594

Asia WGS AF: 0.600 AC: 2086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.80
PhyloP100		0.15
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: rs1474987; hg19: chr6-137185293; COSMIC: COSV59248521;