chr16-48538906-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N4BP1	NM_153029.4	c.*3998C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000262384.4	NP_694574.3
N4BP1	XM_011523482.2	c.*3998C>T		3_prime_UTR_variant	Exon 6 of 6		XP_011521784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
N4BP1	ENST00000262384	c.*3998C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_153029.4	ENSP00000262384.3

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.167

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

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.400

Alfa AF: 0.345 Hom.: 9368

Bravo AF: 0.415

Asia WGS AF: 0.401 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.027
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs1224; hg19: chr16-48572817;