rs3830036

Variant names:

• chr5-171393020-G-A
• rs3830036
• NM_002520.7:c.524+42G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-171393020-G-A
• chr5-171393020-G-C
• chr5-171393020-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002520.7(NPM1):​c.524+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,565,556 control chromosomes in the GnomAD database, including 117,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12449 hom., cov: 32)
  • Exomes 𝑓: 0.38 (104991 hom.)
• Consequence: NPM1 NM_002520.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.547
• Publications: 11 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: Orphanet, G2P
• bone marrow failure syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-171393020-G-A is Benign according to our data. Variant chr5-171393020-G-A is described in ClinVar as Benign. ClinVar VariationId is 1287654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002520.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPM1	NM_002520.7	MANE Select	c.524+42G>A		intron	N/A	NP_002511.1	A0A0S2Z491
	NPM1	NM_001355006.2		c.524+42G>A		intron	N/A	NP_001341935.1	A0A0S2Z491
	NPM1	NM_199185.4		c.524+42G>A		intron	N/A	NP_954654.1	P06748-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPM1	ENST00000296930.10	TSL:1 MANE Select	c.524+42G>A		intron	N/A	ENSP00000296930.5	P06748-1
	NPM1	ENST00000517671.5	TSL:1	c.524+42G>A		intron	N/A	ENSP00000428755.1	P06748-1
	NPM1	ENST00000351986.10	TSL:1	c.524+42G>A		intron	N/A	ENSP00000341168.6	P06748-2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61404 AN: 151782 Hom.: 12427 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.419

GnomAD2 exomes AF: 0.413 AC: 86047 AN: 208460 AF XY: 0.415

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.424

Gnomad EAS exome AF: 0.545

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.381 AC: 538587 AN: 1413656 Hom.: 104991 Cov.: 31 AF XY: 0.384 AC XY: 269873 AN XY: 702220

African (AFR) AF: 0.416 AC: 13290 AN: 31942

American (AMR) AF: 0.407 AC: 15715 AN: 38618

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 10710 AN: 25426

East Asian (EAS) AF: 0.543 AC: 21166 AN: 38964

South Asian (SAS) AF: 0.469 AC: 38270 AN: 81588

European-Finnish (FIN) AF: 0.367 AC: 19168 AN: 52254

Middle Eastern (MID) AF: 0.390 AC: 1975 AN: 5070

European-Non Finnish (NFE) AF: 0.365 AC: 394968 AN: 1081288

Other (OTH) AF: 0.399 AC: 23325 AN: 58506

GnomAD4 genome AF: 0.405 AC: 61471 AN: 151900 Hom.: 12449 Cov.: 32 AF XY: 0.405 AC XY: 30073 AN XY: 74244

African (AFR) AF: 0.418 AC: 17296 AN: 41414

American (AMR) AF: 0.406 AC: 6199 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1475 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2845 AN: 5176

South Asian (SAS) AF: 0.488 AC: 2347 AN: 4808

European-Finnish (FIN) AF: 0.365 AC: 3845 AN: 10530

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26032 AN: 67926

Other (OTH) AF: 0.415 AC: 875 AN: 2108

Alfa AF: 0.401 Hom.: 2791

Bravo AF: 0.407

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.55
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: rs3830036; hg19: chr5-170820024; COSMIC: COSV51543183; COSMIC: COSV51543183;