Genetic Variant NPM1:c.524+42G>A (chr5-171393020-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_002520.7(NPM1):c.524+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,565,556 control chromosomes in the GnomAD database, including 117,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12449 hom., cov: 32)

Exomes 𝑓: 0.38 ( 104991 hom. )

Consequence

NPM1
NM_002520.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.547

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=-0.91).

BP6

Variant 5-171393020-G-A is Benign according to our data. Variant chr5-171393020-G-A is described in ClinVar as [Benign]. Clinvar id is 1287654.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPM1	NM_002520.7 link	c.524+42G>A		intron_variant	Intron 6 of 10	ENST00000296930.10	NP_002511.1	P06748-1A0A0S2Z491

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10 link	c.524+42G>A		intron_variant	Intron 6 of 10	1	NM_002520.7	ENSP00000296930.5		P06748-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61404

AN:

151782

Hom.:

12427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.419

GnomAD3 exomes

AF:

0.413

AC:

86047

AN:

208460

Hom.:

17731

AF XY:

0.415

AC XY:

46524

AN XY:

112232

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.545

Gnomad SAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.381

AC:

538587

AN:

1413656

Hom.:

104991

Cov.:

AF XY:

0.384

AC XY:

269873

AN XY:

702220

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.405

AC:

61471

AN:

151900

Hom.:

12449

Cov.:

AF XY:

0.405

AC XY:

30073

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.488

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.400

Hom.:

2722

Bravo

AF:

0.407

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

DANN

Benign

0.29

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