rs11134697

Variant names:

• chr5-171393312-G-A
• rs11134697
• NM_002520.7:c.524+334G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002520.7(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 NM_002520.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 8 publications found

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]

NPM1 Gene-Disease associations (from GenCC):

• dyskeratosis congenita

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NPM1	NM_002520.7	c.524+334G>A		intron_variant	Intron 6 of 10	ENST00000296930.10	NP_002511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10	c.524+334G>A		intron_variant	Intron 6 of 10	1	NM_002520.7	ENSP00000296930.5

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

African (AFR) AF: 0.715 AC: 29637 AN: 41442

American (AMR) AF: 0.541 AC: 8254 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2115 AN: 3472

East Asian (EAS) AF: 0.551 AC: 2845 AN: 5168

South Asian (SAS) AF: 0.585 AC: 2815 AN: 4814

European-Finnish (FIN) AF: 0.543 AC: 5733 AN: 10550

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37811 AN: 67966

Other (OTH) AF: 0.606 AC: 1278 AN: 2108

Alfa AF: 0.576 Hom.: 43713

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
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11134697; hg19: chr5-170820316;