rs115866467

Variant names:

• chr6-136822635-G-A
• rs115866467
• NM_000288.4:c.-31G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-136822635-G-A
• chr6-136822635-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000288.4(PEX7):​c.-31G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,519,852 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (149 hom., cov: 35)
  • Exomes 𝑓: 0.0025 (134 hom.)
• Consequence: PEX7 NM_000288.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.32
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-136822635-G-A is Benign according to our data. Variant chr6-136822635-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0841 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.-31G>A		5_prime_UTR	Exon 1 of 10	NP_000279.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX7	ENST00000318471.5	TSL:1 MANE Select	c.-31G>A		5_prime_UTR	Exon 1 of 10	ENSP00000315680.3
	PEX7	ENST00000865443.1		c.-31G>A		5_prime_UTR	Exon 1 of 9	ENSP00000535502.1
	PEX7	ENST00000865442.1		c.-31G>A		5_prime_UTR	Exon 1 of 7	ENSP00000535501.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3755 AN: 152220 Hom.: 148 Cov.: 35

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00474 AC: 594 AN: 125200 AF XY: 0.00360

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.00398

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.00245 AC: 3355 AN: 1367516 Hom.: 134 Cov.: 30 AF XY: 0.00212 AC XY: 1433 AN XY: 675358

African (AFR) AF: 0.0918 AC: 2787 AN: 30368

American (AMR) AF: 0.00448 AC: 158 AN: 35288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24746

East Asian (EAS) AF: 0.00 AC: 0 AN: 34914

South Asian (SAS) AF: 0.000140 AC: 11 AN: 78838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33424

Middle Eastern (MID) AF: 0.00288 AC: 13 AN: 4520

European-Non Finnish (NFE) AF: 0.000104 AC: 111 AN: 1068374

Other (OTH) AF: 0.00482 AC: 275 AN: 57044

GnomAD4 genome AF: 0.0247 AC: 3765 AN: 152336 Hom.: 149 Cov.: 35 AF XY: 0.0235 AC XY: 1754 AN XY: 74492

African (AFR) AF: 0.0864 AC: 3593 AN: 41574

American (AMR) AF: 0.00771 AC: 118 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68028

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.00321 Hom.: 5

Bravo AF: 0.0280

Asia WGS AF: 0.00578 AC: 20 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	Peroxisome biogenesis disorder 9B (1)
-	-	1	Rhizomelic chondrodysplasia punctata (1)
-	-	1	Rhizomelic chondrodysplasia punctata type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.27
DANN	Benign	0.80
PhyloP100		-1.3
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs115866467; hg19: chr6-137143773;