5-171388121-G-T

Position:

• chr5-171388121-G-T

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.58+115G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 924,284 control chromosomes in the GnomAD database, including 71,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (12577 hom., cov: 29)
  • Exomes 𝑓: 0.38 (59366 hom.)
• Consequence: NPM1 NM_002520.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0870

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=-0.82).
• BP6: Variant 5-171388121-G-T is Benign according to our data. Variant chr5-171388121-G-T is described in ClinVar as [Benign]. Clinvar id is 1268445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM1	NM_002520.7	c.58+115G>T		intron_variant		ENST00000296930.10	NP_002511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10	c.58+115G>T		intron_variant		1	NM_002520.7	ENSP00000296930	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61524 AN: 151226 Hom.: 12555 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.377 AC: 291366 AN: 772938 Hom.: 59366 AF XY: 0.382 AC XY: 153444 AN XY: 402130

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.407 AC: 61592 AN: 151346 Hom.: 12577 Cov.: 29 AF XY: 0.408 AC XY: 30143 AN XY: 73924

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.419

Alfa AF: 0.239 Hom.: 521

Bravo AF: 0.412

Asia WGS AF: 0.462 AC: 1609 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	-0.82
CADD	Benign	4.0
DANN	Benign	0.53
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3

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: rs2071276; hg19: chr5-170815125;