Genetic Variant NM_014887.3:c.1399G>A (chr13-32522256-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014887.3(N4BP2L2):c.1399G>A(p.Asp467Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,380,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D467H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

N4BP2L2
NM_014887.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.989

Publications

1 publications found

Variant links:

Genes affected

N4BP2L2 (HGNC:26916): (NEDD4 binding protein 2 like 2) Enables enzyme binding activity. Involved in negative regulation of hematopoietic stem cell differentiation and positive regulation of hematopoietic stem cell proliferation. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

N4BP2L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05975327).

BP6

Variant 13-32522256-C-T is Benign according to our data. Variant chr13-32522256-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2611082.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014887.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
N4BP2L2	NM_014887.3	MANE Select	c.1399G>A	p.Asp467Asn	missense	Exon 4 of 6	NP_055702.1	Q92802-1
N4BP2L2	NM_001320836.3		c.1399G>A	p.Asp467Asn	missense	Exon 4 of 10	NP_001307765.1
N4BP2L2	NM_001387001.1		c.1399G>A	p.Asp467Asn	missense	Exon 4 of 10	NP_001373930.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
N4BP2L2	ENST00000267068.6	TSL:1 MANE Select	c.1399G>A	p.Asp467Asn	missense	Exon 4 of 6	ENSP00000267068.3	Q92802-1
N4BP2L2	ENST00000503814.2	TSL:1	n.3793G>A		non_coding_transcript_exon	Exon 1 of 2
N4BP2L2	ENST00000674422.1		c.1399G>A	p.Asp467Asn	missense	Exon 5 of 8	ENSP00000501390.1	A0A6I8PU16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000974

AC:

AN:

205346

AF XY:

0.0000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1380344

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

684906

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29780

American (AMR)

AF:

0.00

AC:

AN:

30878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24014

East Asian (EAS)

AF:

0.00

AC:

AN:

37556

South Asian (SAS)

AF:

0.00

AC:

AN:

69820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.0000186

AC:

AN:

1073808

Other (OTH)

AF:

0.00

AC:

AN:

57092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.59

M_CAP

Benign

0.0080

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.27

PhyloP100

0.99

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.0

REVEL

Benign

0.086

Sift

Benign

0.88

Sift4G

Benign

0.12

Polyphen

0.0020

Vest4

0.14

MutPred

0.25

Gain of catalytic residue at R26 (P = 8e-04)

MVP

0.39

MPC

0.036

ClinPred

0.080

GERP RS

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.31

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over