rs1342645

Variant names:

• chr6-136886166-G-A
• rs1342645
• NM_000288.4:c.804-11976G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-136886166-G-A
• chr6-136886166-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.804-11976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,900 control chromosomes in the GnomAD database, including 13,284 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 0.41 (13284 hom., cov: 31)
• Consequence: PEX7 NM_000288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 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.804-11976G>A		intron	N/A	NP_000279.1	Q6FGN1
	PEX7	NM_001410945.1		c.690-11976G>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.804-11976G>A		intron	N/A	ENSP00000315680.3	O00628-1
	PEX7	ENST00000678557.1		c.690-11976G>A		intron	N/A	ENSP00000502962.1	A0A7I2V2J8
	PEX7	ENST00000865443.1		c.690-11976G>A		intron	N/A	ENSP00000535502.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61639 AN: 151782 Hom.: 13289 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.406 AC: 61650 AN: 151900 Hom.: 13284 Cov.: 31 AF XY: 0.409 AC XY: 30369 AN XY: 74226

African (AFR) AF: 0.248 AC: 10264 AN: 41440

American (AMR) AF: 0.422 AC: 6436 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3466

East Asian (EAS) AF: 0.454 AC: 2343 AN: 5166

South Asian (SAS) AF: 0.508 AC: 2440 AN: 4806

European-Finnish (FIN) AF: 0.482 AC: 5062 AN: 10508

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31902 AN: 67938

Other (OTH) AF: 0.424 AC: 893 AN: 2108

Alfa AF: 0.456 Hom.: 46352

Bravo AF: 0.393

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.72
PhyloP100		2.5
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: rs1342645; hg19: chr6-137207304;