chr5-171400460-CTT-C

Position:

• chr5-171400460-CTT-C

Variant summary

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

The NM_002520.7(NPM1):​c.582+265_582+266del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (8245 hom., cov: 0)
• Consequence: NPM1 NM_002520.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900

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 5-171400460-CTT-C is Benign according to our data. Variant chr5-171400460-CTT-C is described in ClinVar as [Benign]. Clinvar id is 1270281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPM1	NM_002520.7	c.582+265_582+266del		intron_variant		ENST00000296930.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPM1	ENST00000296930.10	c.582+265_582+266del		intron_variant		1	NM_002520.7	P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 49379 AN: 138262 Hom.: 8244 Cov.: 0

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 49384 AN: 138270 Hom.: 8245 Cov.: 0 AF XY: 0.356 AC XY: 23730 AN XY: 66636

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.383

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)		0.010		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: rs199784076; hg19: chr5-170827464;