rs11134697

Positions:

• chr5-171393312-G-A
• chr5-171393312-G-C
• chr5-171393312-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000296930.10(NPM1):​c.524+334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,994 control chromosomes in the GnomAD database, including 27,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27806 hom., cov: 32)
• Consequence: NPM1 ENST00000296930.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM1	NM_002520.7	c.524+334G>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.524+334G>A		intron_variant		1	NM_002520.7	ENSP00000296930	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91198 AN: 151878 Hom.: 27766 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.601 AC: 91292 AN: 151994 Hom.: 27806 Cov.: 32 AF XY: 0.597 AC XY: 44329 AN XY: 74272

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.606

Alfa AF: 0.586 Hom.: 9029

Bravo AF: 0.605

Asia WGS AF: 0.540 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.24

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: rs11134697; hg19: chr5-170820316;