5-171392883-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0830

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]

ACMG classification

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	UniProt
NPM1	NM_002520.7	c.460-31G>A		intron_variant		ENST00000296930.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61352 AN: 151742 Hom.: 12404 Cov.: 31

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

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.: 34 AF XY: 0.387 AC XY: 280431 AN XY: 724032

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.: 31 AF XY: 0.405 AC XY: 30049 AN XY: 74200

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

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

Other links and lift over

dbSNP: rs3830035; hg19: chr5-170819887; COSMIC: COSV51543174; COSMIC: COSV51543174;