4-40126470-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018177.6(N4BP2):​c.4527+140A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 340726 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 174964

African (AFR) AF: 0.00 AC: 0 AN: 8192

American (AMR) AF: 0.00 AC: 0 AN: 8842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10654

East Asian (EAS) AF: 0.00 AC: 0 AN: 23352

South Asian (SAS) AF: 0.00 AC: 0 AN: 16672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1500

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 215888

Other (OTH) AF: 0.00 AC: 0 AN: 19856

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 55

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		0.0060

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;