rs2506887

Positions:

• chr1-10524615-G-A
• chr1-10524615-G-C

Variant summary

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

The NM_004565.3(PEX14):​c.85-11598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 153,436 control chromosomes in the GnomAD database, including 50,506 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 0.81 (50031 hom., cov: 31)
  • Exomes 𝑓: 0.86 (475 hom.)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

Genes affected

PEX14 (HGNC:8856): (peroxisomal biogenesis factor 14) This gene encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. A mutation in this gene results in one form of Zellweger syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX14	NM_004565.3	c.85-11598G>A		intron_variant		ENST00000356607.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX14	ENST00000356607.9	c.85-11598G>A		intron_variant		1	NM_004565.3	P1
PEX14	ENST00000491661.2	c.70-11598G>A		intron_variant		2
PEX14	ENST00000472851.1	n.445+7484G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123180 AN: 152022 Hom.: 50009 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.856 AC: 1109 AN: 1296 Hom.: 475 AF XY: 0.845 AC XY: 558 AN XY: 660

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.808

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.841

GnomAD4 genome AF: 0.810 AC: 123246 AN: 152140 Hom.: 50031 Cov.: 31 AF XY: 0.807 AC XY: 59979 AN XY: 74358

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.804

Alfa AF: 0.817 Hom.: 24348

Bravo AF: 0.810

Asia WGS AF: 0.737 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.25

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: rs2506887; hg19: chr1-10584672;