chr1-160278080-T-A

Position:

chr1-160278080-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000368072.10(PEX19):c.*1471A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 702,516 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 28 hom. )

Consequence

PEX19
ENST00000368072.10 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.421

Variant links:

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]

PEX19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-160278080-T-A is Benign according to our data. Variant chr1-160278080-T-A is described in ClinVar as [Benign]. Clinvar id is 874148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0018 (274/152298) while in subpopulation EAS AF= 0.0268 (139/5186). AF 95% confidence interval is 0.0232. There are 4 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PEX19	NM_002857.4 linkuse as main transcript	c.*1471A>T	3_prime_UTR_variant	8/8	ENST00000368072.10	NP_002848.1
PEX19	NM_001193644.1 linkuse as main transcript	c.*1479A>T	3_prime_UTR_variant	8/8		NP_001180573.1
PEX19	NR_036492.2 linkuse as main transcript	n.2270A>T	non_coding_transcript_exon_variant	7/7
PEX19	NR_036493.2 linkuse as main transcript	n.2294A>T	non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX19	ENST00000368072.10 linkuse as main transcript	c.*1471A>T	3_prime_UTR_variant	8/8	1	NM_002857.4	ENSP00000357051	P1	P40855-1
PEX19	ENST00000472750.5 linkuse as main transcript	c.*2138A>T	3_prime_UTR_variant, NMD_transcript_variant	7/7	1		ENSP00000434633		P40855-6
PEX19	ENST00000467711.5 linkuse as main transcript	n.119+51A>T	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

277

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0271

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00555

AC:

726

AN:

130796

Hom.:

AF XY:

0.00423

AC XY:

302

AN XY:

71408

show subpopulations

Gnomad AFR exome

AF:

0.000329

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0215

Gnomad SAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.00399

GnomAD4 exome

AF:

0.00375

AC:

2064

AN:

550218

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

946

AN XY:

297842

show subpopulations

Gnomad4 AFR exome

AF:

0.000696

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0425

Gnomad4 SAS exome

AF:

0.000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000726

Gnomad4 OTH exome

AF:

0.00160

GnomAD4 genome

AF:

0.00180

AC:

274

AN:

152298

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0268

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000726

Hom.:

Bravo

AF:

0.00286

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Peroxisome biogenesis disorder 12A (Zellweger)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over