rs4970989

Positions:

• chr1-151031124-T-A
• chr1-151031124-T-C
• chr1-151031124-T-G

Variant summary

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

The NM_021222.3(PRUNE1):​c.933+2180T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 150,876 control chromosomes in the GnomAD database, including 36,910 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 0.68 (36910 hom., cov: 27)
• Consequence: PRUNE1 NM_021222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

PRUNE1 (HGNC:13420): (prune exopolyphosphatase 1) This gene encodes a member of the DHH protein superfamily of phosphoesterases. This protein has been found to function as both a nucleotide phosphodiesterase and an exopolyphosphatase. This protein is believed to stimulate cancer progression and metastases through the induction of cell motility. A pseuodgene has been identified on chromosome 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRUNE1	NM_021222.3	c.933+2180T>A		intron_variant		ENST00000271620.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRUNE1	ENST00000271620.8	c.933+2180T>A		intron_variant		1	NM_021222.3	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102159 AN: 150768 Hom.: 36914 Cov.: 27

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.677 AC: 102181 AN: 150876 Hom.: 36910 Cov.: 27 AF XY: 0.680 AC XY: 50051 AN XY: 73558

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.724

Alfa AF: 0.713 Hom.: 4995

Bravo AF: 0.669

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.74

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: rs4970989; hg19: chr1-151003600;