6-136895709-A-T

Variant names:

• chr6-136895709-A-T
• rs1012515
• NM_000288.4:c.804-2433A>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.804-2433A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,058 control chromosomes in the GnomAD database, including 18,983 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 0.50 (18983 hom., cov: 32)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• rhizomelic chondrodysplasia punctata type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX7	NM_000288.4	c.804-2433A>T		intron_variant	Intron 8 of 9	ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.690-2433A>T		intron_variant	Intron 8 of 9		NP_001397874.1
PEX7	XM_006715502.3	c.510-2433A>T		intron_variant	Intron 5 of 6		XP_006715565.1
PEX7	XM_047418874.1	c.527-2433A>T		intron_variant	Intron 5 of 5		XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.804-2433A>T		intron_variant	Intron 8 of 9	1	NM_000288.4	ENSP00000315680.3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75688 AN: 151940 Hom.: 18969 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.498 AC: 75750 AN: 152058 Hom.: 18983 Cov.: 32 AF XY: 0.499 AC XY: 37107 AN XY: 74314

African (AFR) AF: 0.500 AC: 20745 AN: 41460

American (AMR) AF: 0.462 AC: 7056 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3472

East Asian (EAS) AF: 0.489 AC: 2534 AN: 5180

South Asian (SAS) AF: 0.567 AC: 2735 AN: 4820

European-Finnish (FIN) AF: 0.509 AC: 5370 AN: 10558

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33852 AN: 67978

Other (OTH) AF: 0.500 AC: 1055 AN: 2112

Alfa AF: 0.498 Hom.: 2454

Bravo AF: 0.494

Asia WGS AF: 0.583 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.55
PhyloP100		-0.0010
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: rs1012515; hg19: chr6-137216847; COSMIC: COSV59248626; COSMIC: COSV59248626;