Genetic Variant N4BP1:p.Arg814Gln (chr16-48543154-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153029.4(N4BP1):c.2441G>A(p.Arg814Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,603,822 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 52 hom. )

Consequence

N4BP1
NM_153029.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.928

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004618764).

BP6

Variant 16-48543154-C-T is Benign according to our data. Variant chr16-48543154-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646501.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N4BP1	NM_153029.4 link	c.2441G>A	p.Arg814Gln	missense_variant	Exon 7 of 7	ENST00000262384.4	NP_694574.3	O75113
N4BP1	XM_011523482.2 link	c.2333G>A	p.Arg778Gln	missense_variant	Exon 6 of 6		XP_011521784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
N4BP1	ENST00000262384.4 link	c.2441G>A	p.Arg814Gln	missense_variant	Exon 7 of 7	1	NM_153029.4	ENSP00000262384.3	O75113
N4BP1	ENST00000565423.5 link	n.275G>A		non_coding_transcript_exon_variant	Exon 3 of 3	4
N4BP1	ENST00000569027.1 link	n.*10G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

950

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0372

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00623

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00715

AC:

1753

AN:

245084

Hom.:

AF XY:

0.00684

AC XY:

910

AN XY:

133094

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.00790

Gnomad ASJ exome

AF:

0.00267

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000465

Gnomad FIN exome

AF:

0.0355

Gnomad NFE exome

AF:

0.00583

Gnomad OTH exome

AF:

0.00422

GnomAD4 exome

AF:

0.00575

AC:

8346

AN:

1451518

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

4026

AN XY:

719868

show subpopulations

Gnomad4 AFR exome

AF:

0.000901

Gnomad4 AMR exome

AF:

0.00679

Gnomad4 ASJ exome

AF:

0.00197

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000606

Gnomad4 FIN exome

AF:

0.0329

Gnomad4 NFE exome

AF:

0.00531

Gnomad4 OTH exome

AF:

0.00483

GnomAD4 genome

AF:

0.00624

AC:

951

AN:

152304

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

548

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0372

Gnomad4 NFE

AF:

0.00623

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00535

Hom.:

Bravo

AF:

0.00391

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000996

AC:

ESP6500EA

AF:

0.00501

AC:

ExAC

AF:

0.00626

AC:

757

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

N4BP1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.71

REVEL

Benign

0.062

Sift

Benign

0.12

Sift4G

Benign

0.42

Polyphen

1.0

Vest4

0.082

MVP

0.60

MPC

0.29

ClinPred

0.014

GERP RS

4.2

Varity_R

0.071

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over