1-160277395-G-C

Variant names:

• chr1-160277395-G-C
• rs10594
• ENST00000472750.5:n.*2823C>G

Variant summary

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

The ENST00000472750.5(PEX19):​n.*2823C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 455,818 control chromosomes in the GnomAD database, including 56,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16145 hom., cov: 32)
  • Exomes 𝑓: 0.51 (39923 hom.)
• Consequence: PEX19 ENST00000472750.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.465
• Publications: 23 publications found

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]

ENSG00000258465 (HGNC:):

DCAF8-DT (HGNC:55792): (DCAF8 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-160277395-G-C is Benign according to our data. Variant chr1-160277395-G-C is described in ClinVar as Benign. ClinVar VariationId is 293196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472750.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX19	NM_002857.4	MANE Select	c.*2156C>G		3_prime_UTR	Exon 8 of 8	NP_002848.1
	PEX19	NR_036492.2		n.2955C>G		non_coding_transcript_exon	Exon 7 of 7
	PEX19	NR_036493.2		n.2979C>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX19	ENST00000472750.5	TSL:1	n.*2823C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000434633.1
	PEX19	ENST00000368072.10	TSL:1 MANE Select	c.*2156C>G		3_prime_UTR	Exon 8 of 8	ENSP00000357051.5
	PEX19	ENST00000472750.5	TSL:1	n.*2823C>G		3_prime_UTR	Exon 7 of 7	ENSP00000434633.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69175 AN: 151946 Hom.: 16142 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.482

GnomAD2 exomes AF: 0.495 AC: 63464 AN: 128218 AF XY: 0.503

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.348

Gnomad FIN exome AF: 0.485

Gnomad NFE exome AF: 0.507

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.507 AC: 154061 AN: 303754 Hom.: 39923 Cov.: 0 AF XY: 0.518 AC XY: 89580 AN XY: 172980

African (AFR) AF: 0.340 AC: 2931 AN: 8620

American (AMR) AF: 0.483 AC: 13169 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 4743 AN: 10786

East Asian (EAS) AF: 0.347 AC: 3198 AN: 9210

South Asian (SAS) AF: 0.610 AC: 36454 AN: 59736

European-Finnish (FIN) AF: 0.472 AC: 5838 AN: 12364

Middle Eastern (MID) AF: 0.486 AC: 1350 AN: 2776

European-Non Finnish (NFE) AF: 0.500 AC: 79408 AN: 158772

Other (OTH) AF: 0.490 AC: 6970 AN: 14216

GnomAD4 genome AF: 0.455 AC: 69214 AN: 152064 Hom.: 16145 Cov.: 32 AF XY: 0.456 AC XY: 33905 AN XY: 74328

African (AFR) AF: 0.350 AC: 14524 AN: 41468

American (AMR) AF: 0.477 AC: 7296 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1793 AN: 5182

South Asian (SAS) AF: 0.609 AC: 2939 AN: 4828

European-Finnish (FIN) AF: 0.500 AC: 5271 AN: 10532

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34262 AN: 67984

Other (OTH) AF: 0.483 AC: 1021 AN: 2112

Alfa AF: 0.466 Hom.: 3007

Bravo AF: 0.448

Asia WGS AF: 0.477 AC: 1657 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Peroxisome biogenesis disorder 12A (Zellweger) Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs10594; hg19: chr1-160247185; COSMIC: COSV63619513; COSMIC: COSV63619513;