5-171387358-A-T

Position:

• chr5-171387358-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000517671.5(NPM1):​c.-17+124A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 160,352 control chromosomes in the GnomAD database, including 556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (534 hom., cov: 31)
  • Exomes 𝑓: 0.052 (22 hom.)
• Consequence: NPM1 ENST00000517671.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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=-0.76).
• BP6: Variant 5-171387358-A-T is Benign according to our data. Variant chr5-171387358-A-T is described in ClinVar as [Benign]. Clinvar id is 1261516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM1	NM_001355006.2	c.-17+124A>T		intron_variant			NP_001341935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000517671.5	c.-17+124A>T		intron_variant		1		ENSP00000428755	P1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9709 AN: 152150 Hom.: 523 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.00971

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0523

GnomAD4 exome AF: 0.0520 AC: 420 AN: 8084 Hom.: 22 AF XY: 0.0518 AC XY: 200 AN XY: 3862

Gnomad4 AFR exome AF: 0.0950

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.0343

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.0640 AC: 9751 AN: 152268 Hom.: 534 Cov.: 31 AF XY: 0.0662 AC XY: 4931 AN XY: 74456

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.00971

Gnomad4 NFE AF: 0.0258

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0464 Hom.: 43

Bravo AF: 0.0768

Asia WGS AF: 0.115 AC: 401 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.88

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: rs11134695; hg19: chr5-170814362;