rs1342645

Positions:

• chr6-136886166-G-A
• chr6-136886166-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.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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX7	NM_000288.4	c.804-11976G>A		intron_variant		ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.690-11976G>A		intron_variant			NP_001397874.1
PEX7	XM_006715502.3	c.510-11976G>A		intron_variant			XP_006715565.1
PEX7	XM_047418874.1	c.527-11976G>A		intron_variant			XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.804-11976G>A		intron_variant		1	NM_000288.4	ENSP00000315680	P1

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

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.424

Alfa AF: 0.461 Hom.: 32591

Bravo AF: 0.393

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.72

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: rs1342645; hg19: chr6-137207304;