Variant 5-171400111-C-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 ENST00000296930.10(NPM1):c.525-42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,187,012 control chromosomes in the GnomAD database, including 92,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12271 hom., cov: 32)

Exomes 𝑓: 0.39 ( 79812 hom. )

Consequence

NPM1
ENST00000296930.10 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.77

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=-0.9).

BP6

Variant 5-171400111-C-A is Benign according to our data. Variant chr5-171400111-C-A is described in ClinVar as [Benign]. Clinvar id is 1226494.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	Protein	UniProt
NPM1	NM_002520.7 linkuse as main transcript	c.525-42C>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.525-42C>A		intron_variant		1	NM_002520.7	ENSP00000296930	P1	P06748-1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61060

AN:

151446

Hom.:

12248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.506

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.415

GnomAD3 exomes

AF:

0.411

AC:

99260

AN:

241676

Hom.:

20432

AF XY:

0.413

AC XY:

53980

AN XY:

130832

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.543

Gnomad SAS exome

AF:

0.474

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.388

AC:

402239

AN:

1035450

Hom.:

79812

Cov.:

AF XY:

0.392

AC XY:

209354

AN XY:

533748

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.549

Gnomad4 SAS exome

AF:

0.470

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.403

AC:

61129

AN:

151562

Hom.:

12271

Cov.:

AF XY:

0.404

AC XY:

29893

AN XY:

74052

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.547

Gnomad4 SAS

AF:

0.488

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.382

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.337

Hom.:

1810

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0080

DANN

Benign

0.65

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