dbSNP rs34351976: NPM1:c.*165delT (chr5-171410729-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002520.7(NPM1):c.*165delT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.326 in 509,706 control chromosomes in the GnomAD database, including 29,164 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6957 hom., cov: 21)

Exomes 𝑓: 0.35 ( 22207 hom. )

Consequence

NPM1
NM_002520.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83

Publications

6 publications found

Variant links:

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

NPM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPM1	NM_002520.7 link	c.*165delT		3_prime_UTR_variant	Exon 11 of 11	ENST00000296930.10	NP_002511.1	P06748-1A0A0S2Z491

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10 link	c.*165delT		3_prime_UTR_variant	Exon 11 of 11	1	NM_002520.7	ENSP00000296930.5		P06748-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42762

AN:

151790

Hom.:

6956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.345

AC:

123500

AN:

357798

Hom.:

22207

Cov.:

AF XY:

0.348

AC XY:

65400

AN XY:

188166

show subpopulations

African (AFR)

AF:

0.117

AC:

1115

AN:

9556

American (AMR)

AF:

0.218

AC:

2399

AN:

10988

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

4345

AN:

11732

East Asian (EAS)

AF:

0.427

AC:

11492

AN:

26918

South Asian (SAS)

AF:

0.351

AC:

9024

AN:

25730

European-Finnish (FIN)

AF:

0.359

AC:

9349

AN:

26058

Middle Eastern (MID)

AF:

0.336

AC:

576

AN:

1712

European-Non Finnish (NFE)

AF:

0.349

AC:

78000

AN:

223352

Other (OTH)

AF:

0.331

AC:

7200

AN:

21752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3836

7671

11507

15342

19178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.281

AC:

42761

AN:

151908

Hom.:

6957

Cov.:

AF XY:

0.281

AC XY:

20842

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.114

AC:

4742

AN:

41462

American (AMR)

AF:

0.237

AC:

3615

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1294

AN:

3466

East Asian (EAS)

AF:

0.429

AC:

2212

AN:

5152

South Asian (SAS)

AF:

0.373

AC:

1795

AN:

4810

European-Finnish (FIN)

AF:

0.354

AC:

3723

AN:

10512

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24172

AN:

67916

Other (OTH)

AF:

0.313

AC:

661

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1500

2999

4499

5998

7498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.206

Hom.:

530

Bravo

AF:

0.264

Asia WGS

AF:

0.322

AC:

1120

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.8

Mutation Taster

=100/0

polymorphism

(source)

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

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rs34351976

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over