chr5-171392603-T-A

Position:

• chr5-171392603-T-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.353-107T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 549,514 control chromosomes in the GnomAD database, including 43,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9299 hom., cov: 29)
  • Exomes 𝑓: 0.40 (34344 hom.)
• Consequence: NPM1 NM_002520.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.780

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=-0.83).
• BP6: Variant 5-171392603-T-A is Benign according to our data. Variant chr5-171392603-T-A is described in ClinVar as [Benign]. Clinvar id is 1280200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM1	NM_002520.7	c.353-107T>A		intron_variant		ENST00000296930.10	NP_002511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10	c.353-107T>A		intron_variant		1	NM_002520.7	ENSP00000296930	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 51727 AN: 148694 Hom.: 9304 Cov.: 29

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.400 AC: 160108 AN: 400736 Hom.: 34344 AF XY: 0.402 AC XY: 82922 AN XY: 206132

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.428

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.348 AC: 51723 AN: 148778 Hom.: 9299 Cov.: 29 AF XY: 0.347 AC XY: 25140 AN XY: 72492

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.383

Alfa AF: 0.363 Hom.: 1129

Bravo AF: 0.338

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	-0.83
CADD	Benign	1.3
DANN	Benign	0.11

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: rs60056043; hg19: chr5-170819607; COSMIC: COSV51551188; COSMIC: COSV51551188;