rs2252352

Variant names:

• chr4-40126470-A-G
• rs2252352
• NM_018177.6:c.4527+140A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-40126470-A-G
• chr4-40126470-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018177.6(N4BP2):​c.4527+140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 492,734 control chromosomes in the GnomAD database, including 4,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (941 hom., cov: 32)
  • Exomes 𝑓: 0.080 (3097 hom.)
• Consequence: N4BP2 NM_018177.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 1 publications found

Genes affected

N4BP2 (HGNC:29851): (NEDD4 binding protein 2) This gene encodes a protein containing a polynucleotide kinase domain (PNK) near the N-terminal region, and a Small MutS Related (Smr) domain near the C-terminal region. The encoded protein can bind to both B-cell leukemia/lymphoma 3 (BCL-3) and neural precursor cell expressed, developmentally downregulated 4, (Nedd4) proteins. This protein binds and hydrolyzes ATP, may function as a 5'-polynucleotide kinase, and has the capacity to be a ubiquitylation substrate. This protein may play a role in transcription-coupled DNA repair or genetic recombination. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018177.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP2	NM_018177.6	MANE Select	c.4527+140A>G		intron	N/A	NP_060647.2
	N4BP2	NM_001318359.2		c.4287+140A>G		intron	N/A	NP_001305288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP2	ENST00000261435.11	TSL:5 MANE Select	c.4527+140A>G		intron	N/A	ENSP00000261435.6
	N4BP2	ENST00000513269.1	TSL:1	c.3465+140A>G		intron	N/A	ENSP00000426430.1
	N4BP2	ENST00000511480.5	TSL:1	n.*4318+140A>G		intron	N/A	ENSP00000422436.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12443 AN: 152120 Hom.: 939 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0831

GnomAD4 exome AF: 0.0796 AC: 27104 AN: 340496 Hom.: 3097 AF XY: 0.0806 AC XY: 14088 AN XY: 174836

African (AFR) AF: 0.106 AC: 868 AN: 8190

American (AMR) AF: 0.0678 AC: 599 AN: 8832

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 837 AN: 10646

East Asian (EAS) AF: 0.453 AC: 10557 AN: 23298

South Asian (SAS) AF: 0.144 AC: 2393 AN: 16630

European-Finnish (FIN) AF: 0.0220 AC: 787 AN: 35758

Middle Eastern (MID) AF: 0.103 AC: 155 AN: 1498

European-Non Finnish (NFE) AF: 0.0436 AC: 9408 AN: 215800

Other (OTH) AF: 0.0756 AC: 1500 AN: 19844

GnomAD4 genome AF: 0.0819 AC: 12462 AN: 152238 Hom.: 941 Cov.: 32 AF XY: 0.0845 AC XY: 6292 AN XY: 74454

African (AFR) AF: 0.117 AC: 4859 AN: 41526

American (AMR) AF: 0.0675 AC: 1031 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2115 AN: 5176

South Asian (SAS) AF: 0.158 AC: 764 AN: 4830

European-Finnish (FIN) AF: 0.0261 AC: 277 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2908 AN: 68020

Other (OTH) AF: 0.0865 AC: 183 AN: 2116

Alfa AF: 0.0522 Hom.: 55

Bravo AF: 0.0879

Asia WGS AF: 0.242 AC: 842 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.81
PhyloP100		0.0060
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: rs2252352; hg19: chr4-40128090;