Variant chr5-171400114-A-G 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.525-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,232,158 control chromosomes in the GnomAD database, including 95,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12275 hom., cov: 32)

Exomes 𝑓: 0.39 ( 82839 hom. )

Consequence

NPM1
NM_002520.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-171400114-A-G is Benign according to our data. Variant chr5-171400114-A-G is described in ClinVar as [Benign]. Clinvar id is 1290345.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPM1	NM_002520.7 linkuse as main transcript	c.525-39A>G		intron_variant		ENST00000296930.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPM1	ENST00000296930.10 linkuse as main transcript	c.525-39A>G		intron_variant		1	NM_002520.7	P1	P06748-1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61075

AN:

151564

Hom.:

12252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.411

AC:

99668

AN:

242624

Hom.:

20521

AF XY:

0.413

AC XY:

54201

AN XY:

131340

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.543

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.386

AC:

416997

AN:

1080474

Hom.:

82839

Cov.:

AF XY:

0.390

AC XY:

216308

AN XY:

554914

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.545

Gnomad4 SAS exome

AF:

0.470

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.403

AC:

61144

AN:

151684

Hom.:

12275

Cov.:

AF XY:

0.403

AC XY:

29899

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.547

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.382

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.404

Hom.:

2352

Bravo

AF:

0.407

Asia WGS

AF:

0.459

AC:

1599

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

-0.91

CADD

Benign

7.3

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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