rs2012700

Variant names:

• chr6-136858249-G-A
• rs2012700
• NM_000288.4:c.527-8378G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_000288.4(PEX7):​c.527-8378G>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
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 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.527-8378G>A		intron	N/A	NP_000279.1	Q6FGN1
	PEX7	NM_001410945.1		c.413-8378G>A		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.527-8378G>A		intron	N/A	ENSP00000315680.3	O00628-1
	PEX7	ENST00000678557.1		c.413-8378G>A		intron	N/A	ENSP00000502962.1	A0A7I2V2J8
	PEX7	ENST00000865443.1		c.527-8378G>A		intron	N/A	ENSP00000535502.1

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

African (AFR) AF: 0.697 AC: 28926 AN: 41490

American (AMR) AF: 0.635 AC: 9692 AN: 15268

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

East Asian (EAS) AF: 0.531 AC: 2753 AN: 5180

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4826

European-Finnish (FIN) AF: 0.586 AC: 6189 AN: 10560

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42568 AN: 67964

Other (OTH) AF: 0.632 AC: 1329 AN: 2102

Alfa AF: 0.630 Hom.: 91467

Bravo AF: 0.642

Asia WGS AF: 0.632 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.29
PhyloP100		0.56
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: rs2012700; hg19: chr6-137179387;