rs2820421

Variant names:

• chr1-160286214-C-A
• rs2820421
• ENST00000533699.5:n.64+71G>T

Variant summary

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

The ENST00000533699.5(PEX19):​n.64+71G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,110 control chromosomes in the GnomAD database, including 32,968 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 0.64 (32962 hom., cov: 32)
  • Exomes 𝑓: 0.59 (6 hom.)
• Consequence: PEX19 ENST00000533699.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

Genes affected

PEX19 (HGNC:9713): (peroxisomal biogenesis factor 19) This gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. These disorders have at least 14 complementation groups, with more than one phenotype being observed for some 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 are a cause of Zellweger syndrome (ZWS), as well as peroxisome biogenesis disorder complementation group 14 (PBD-CG14), which is also known as PBD-CGJ. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

LOC107985219 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985219	XR_001738265.2	n.492-103C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX19	ENST00000533699.5	n.64+71G>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97668 AN: 151958 Hom.: 32913 Cov.: 32

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.588 AC: 20 AN: 34 Hom.: 6 AF XY: 0.550 AC XY: 11 AN XY: 20

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.615

GnomAD4 genome AF: 0.643 AC: 97776 AN: 152076 Hom.: 32962 Cov.: 32 AF XY: 0.640 AC XY: 47557 AN XY: 74336

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.639

Alfa AF: 0.582 Hom.: 13998

Bravo AF: 0.654

Asia WGS AF: 0.630 AC: 2193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2820421; hg19: chr1-160256004;