rs148110587

Variant names:

• chr16-48543154-C-T
• rs148110587
• NM_153029.4:c.2441G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 12/20 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. R814W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0062 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (52 hom.)
• Consequence: N4BP1 NM_153029.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.928
• Publications: 3 publications found

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]

ENSG00000295475 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2646501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.2441G>A	p.Arg814Gln	missense	Exon 7 of 7	NP_694574.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP1	ENST00000262384.4	TSL:1 MANE Select	c.2441G>A	p.Arg814Gln	missense	Exon 7 of 7	ENSP00000262384.3	O75113
	N4BP1	ENST00000962631.1		c.2564G>A	p.Arg855Gln	missense	Exon 8 of 8	ENSP00000632690.1
	N4BP1	ENST00000934852.1		c.2552G>A	p.Arg851Gln	missense	Exon 8 of 8	ENSP00000604911.1

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 950 AN: 152186 Hom.: 5 Cov.: 33

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

GnomAD2 exomes AF: 0.00715 AC: 1753 AN: 245084 AF XY: 0.00684

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 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.: 52 Cov.: 31 AF XY: 0.00559 AC XY: 4026 AN XY: 719868

African (AFR) AF: 0.000901 AC: 30 AN: 33312

American (AMR) AF: 0.00679 AC: 301 AN: 44340

Ashkenazi Jewish (ASJ) AF: 0.00197 AC: 51 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.000606 AC: 52 AN: 85802

European-Finnish (FIN) AF: 0.0329 AC: 1751 AN: 53196

Middle Eastern (MID) AF: 0.00123 AC: 7 AN: 5714

European-Non Finnish (NFE) AF: 0.00531 AC: 5865 AN: 1104068

Other (OTH) AF: 0.00483 AC: 289 AN: 59840

GnomAD4 genome AF: 0.00624 AC: 951 AN: 152304 Hom.: 5 Cov.: 33 AF XY: 0.00736 AC XY: 548 AN XY: 74474

African (AFR) AF: 0.00118 AC: 49 AN: 41578

American (AMR) AF: 0.00445 AC: 68 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0372 AC: 395 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00623 AC: 424 AN: 68020

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00477 Hom.: 12

Bravo AF: 0.00391

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000996 AC: 4

ESP6500EA AF: 0.00501 AC: 42

ExAC AF: 0.00626 AC: 757

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.93
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.062
Sift	Benign	0.12	T
Sift4G	Benign	0.42	T
Polyphen		1.0	D
Vest4		0.082
MVP		0.60
MPC		0.29
ClinPred		0.014	T
GERP RS		4.2
Varity_R		0.071
Mutation Taster		=98/2	polymorphism

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: rs148110587; hg19: chr16-48577065;