5-171400111-C-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.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 NM_002520.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77

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=-0.9).
• 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	UniProt
NPM1	NM_002520.7	c.525-42C>A		intron_variant		ENST00000296930.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPM1	ENST00000296930.10	c.525-42C>A		intron_variant		1	NM_002520.7	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61060 AN: 151446 Hom.: 12248 Cov.: 32

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

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.: 14 AF XY: 0.392 AC XY: 209354 AN XY: 533748

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.: 32 AF XY: 0.404 AC XY: 29893 AN XY: 74052

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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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

Other links and lift over

dbSNP: rs6555952; hg19: chr5-170827115; COSMIC: COSV51545512; COSMIC: COSV51545512;