chr5-171392586-CTTT-C

Position:

• chr5-171392586-CTTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002520.7(NPM1):​c.353-109_353-107del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 449,836 control chromosomes in the GnomAD database, including 16,249 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (9811 hom., cov: 0)
  • Exomes 𝑓: 0.35 (6438 hom.)
• Consequence: NPM1 NM_002520.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.718

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 -10 ACMG points.

• BP6: Variant 5-171392586-CTTT-C is Benign according to our data. Variant chr5-171392586-CTTT-C is described in ClinVar as [Benign]. Clinvar id is 1277189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPM1	NM_002520.7	c.353-109_353-107del		intron_variant		ENST00000296930.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPM1	ENST00000296930.10	c.353-109_353-107del		intron_variant		1	NM_002520.7	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 53479 AN: 142548 Hom.: 9804 Cov.: 0

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.345 AC: 106148 AN: 307242 Hom.: 6438 AF XY: 0.347 AC XY: 55131 AN XY: 158688

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.406

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.375 AC: 53505 AN: 142594 Hom.: 9811 Cov.: 0 AF XY: 0.377 AC XY: 26018 AN XY: 69012

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.409

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs34475806; hg19: chr5-170819590;