rs1224

Variant names:

• chr16-48538906-G-A
• rs1224
• NM_153029.4:c.*3998C>T

Variant summary

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

The NM_153029.4(N4BP1):​c.*3998C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,084 control chromosomes in the GnomAD database, including 13,599 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 0.41 (13592 hom., cov: 32)
  • Exomes 𝑓: 0.34 (7 hom.)
• Consequence: N4BP1 NM_153029.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

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.*3998C>T		3_prime_UTR	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.*3998C>T		3_prime_UTR	Exon 7 of 7	ENSP00000262384.3	O75113
	ENSG00000295475	ENST00000730325.1		n.480+11688G>A		intron	N/A
	ENSG00000295475	ENST00000730326.1		n.162+11688G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61719 AN: 151868 Hom.: 13570 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.337 AC: 33 AN: 98 Hom.: 7 Cov.: 0 AF XY: 0.350 AC XY: 28 AN XY: 80

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.313 AC: 25 AN: 80

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.407 AC: 61790 AN: 151986 Hom.: 13592 Cov.: 32 AF XY: 0.410 AC XY: 30416 AN XY: 74264

African (AFR) AF: 0.575 AC: 23848 AN: 41464

American (AMR) AF: 0.424 AC: 6475 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1266 AN: 5140

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4814

European-Finnish (FIN) AF: 0.414 AC: 4370 AN: 10552

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21602 AN: 67948

Other (OTH) AF: 0.400 AC: 846 AN: 2114

Alfa AF: 0.357 Hom.: 15013

Bravo AF: 0.415

Asia WGS AF: 0.401 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.027
DANN	Benign	0.76
PhyloP100		-2.0
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: rs1224; hg19: chr16-48572817;