Genetic Variant NM_153029.4:c.1844C>T (chr16-48560799-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153029.4(N4BP1):c.1844C>T(p.Thr615Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,612,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

N4BP1
NM_153029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Publications

2 publications found

Variant links:

Genes affected

N4BP1 (HGNC:29850): (NEDD4 binding protein 1) Enables mRNA binding activity; ribonuclease activity; and ubiquitin binding activity. Involved in cellular response to UV and negative regulation of viral genome replication. Predicted to be located in cytosol and nucleolus. Predicted to be active in PML body. [provided by Alliance of Genome Resources, Apr 2022]

N4BP1 links:

ENSG00000261267 (HGNC:):

ENSG00000261267 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.06338397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153029.4. 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
	N4BP1	NM_153029.4	MANE Select	c.1844C>T	p.Thr615Met	missense	Exon 2 of 7	NP_694574.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
N4BP1	ENST00000262384.4	TSL:1 MANE Select	c.1844C>T	p.Thr615Met	missense	Exon 2 of 7	ENSP00000262384.3	O75113
N4BP1	ENST00000962631.1		c.1844C>T	p.Thr615Met	missense	Exon 2 of 8	ENSP00000632690.1
N4BP1	ENST00000934852.1		c.1955C>T	p.Thr652Met	missense	Exon 3 of 8	ENSP00000604911.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000165

AC:

AN:

247986

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.000601

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000190

AC:

278

AN:

1460594

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

145

AN XY:

726604

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33408

American (AMR)

AF:

0.000360

AC:

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.000538

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000207

AC:

230

AN:

1111494

Other (OTH)

AF:

0.000216

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

AF:

0.000151

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41418

American (AMR)

AF:

0.000196

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.063

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.4

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.062

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.14

M_CAP

Benign

0.013

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.7

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.029

Sift

Benign

0.12

Sift4G

Benign

0.076

Polyphen

0.82

Vest4

0.15

MVP

0.50

MPC

0.14

ClinPred

0.030

GERP RS

2.9

Varity_R

0.019

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over