5-171400114-A-G

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.38

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=-0.91).
• 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	c.525-39A>G		intron_variant		ENST00000296930.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61075 AN: 151564 Hom.: 12252 Cov.: 32

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

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.: 15 AF XY: 0.390 AC XY: 216308 AN XY: 554914

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.: 32 AF XY: 0.403 AC XY: 29899 AN XY: 74104

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

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

Other links and lift over

dbSNP: rs6555953; hg19: chr5-170827118; COSMIC: COSV51545531; COSMIC: COSV51545531;