Variant 5-171392883-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002520.7(NPM1):c.460-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,606,498 control chromosomes in the GnomAD database, including 121,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12426 hom., cov: 31)

Exomes 𝑓: 0.38 ( 109441 hom. )

Consequence

NPM1
NM_002520.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0830

Variant links:

Genes affected

NPM1 (HGNC:7910): (nucleophosmin 1) The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]

NPM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-171392883-G-A is Benign according to our data. Variant chr5-171392883-G-A is described in ClinVar as [Benign]. Clinvar id is 1275969.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM1	NM_002520.7 linkuse as main transcript	c.460-31G>A		intron_variant		ENST00000296930.10	NP_002511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10 linkuse as main transcript	c.460-31G>A		intron_variant		1	NM_002520.7	ENSP00000296930	P1	P06748-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61352

AN:

151742

Hom.:

12404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.415

GnomAD3 exomes

AF:

0.412

AC:

103312

AN:

250982

Hom.:

21707

AF XY:

0.414

AC XY:

56168

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.545

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.384

AC:

558643

AN:

1454638

Hom.:

109441

Cov.:

AF XY:

0.387

AC XY:

280431

AN XY:

724032

show subpopulations

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.401

GnomAD4 genome

AF:

0.404

AC:

61419

AN:

151860

Hom.:

12426

Cov.:

AF XY:

0.405

AC XY:

30049

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.549

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.401

Hom.:

2721

Bravo

AF:

0.407

Asia WGS

AF:

0.458

AC:

1596

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.7

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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