6-136895709-A-T

Position:

• chr6-136895709-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000318471.5(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 ENST00000318471.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.96).
• 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/exons	MANE	Protein	UniProt
PEX7	NM_000288.4	c.804-2433A>T		intron_variant		ENST00000318471.5	NP_000279.1
PEX7	NM_001410945.1	c.690-2433A>T		intron_variant			NP_001397874.1
PEX7	XM_006715502.3	c.510-2433A>T		intron_variant			XP_006715565.1
PEX7	XM_047418874.1	c.527-2433A>T		intron_variant			XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.804-2433A>T		intron_variant		1	NM_000288.4	ENSP00000315680	P1

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

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.500

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

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: rs1012515; hg19: chr6-137216847; COSMIC: COSV59248626; COSMIC: COSV59248626;