8-31033432-C-G

Position:

• chr8-31033432-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000339382.3(PURG):​c.-650G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 154,414 control chromosomes in the GnomAD database, including 952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (951 hom., cov: 30)
  • Exomes 𝑓: 0.034 (1 hom.)
• Consequence: PURG ENST00000339382.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11

Genes affected

PURG (HGNC:17930): (purine rich element binding protein G) The exact function of this gene is not known, however, its encoded product is highly similar to purine-rich element binding protein A. The latter is a DNA-binding protein which binds preferentially to the single strand of the purine-rich element termed PUR, and has been implicated in the control of both DNA replication and transcription. This gene lies in close proximity to the Werner syndrome gene, but on the opposite strand, on chromosome 8p11. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-31033432-C-G is Benign according to our data. Variant chr8-31033432-C-G is described in ClinVar as [Benign]. Clinvar id is 362775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURG	ENST00000339382.3	c.-650G>C		5_prime_UTR_variant	1/2	1
PURG	ENST00000475541.2	c.-650G>C		5_prime_UTR_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12430 AN: 151574 Hom.: 951 Cov.: 30

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0683

GnomAD4 exome AF: 0.0337 AC: 92 AN: 2726 Hom.: 1 Cov.: 0 AF XY: 0.0388 AC XY: 63 AN XY: 1622

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0429

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0494

GnomAD4 genome AF: 0.0821 AC: 12452 AN: 151688 Hom.: 951 Cov.: 30 AF XY: 0.0778 AC XY: 5770 AN XY: 74148

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000586

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.0369

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0655 Hom.: 77

Bravo AF: 0.0867

Asia WGS AF: 0.0250 AC: 88 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Werner syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.4
DANN	Benign	0.57

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: rs7017069; hg19: chr8-30890948;