rs6500395

Variant names:

• chr16-48587491-T-C
• rs6500395
• NM_153029.4:c.198+22284A>G

Variant summary

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

The NM_153029.4(N4BP1):​c.198+22284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,068 control chromosomes in the GnomAD database, including 13,538 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 (13538 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: N4BP1 NM_153029.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 17 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N4BP1	NM_153029.4	c.198+22284A>G		intron_variant	Intron 1 of 6	ENST00000262384.4	NP_694574.3
N4BP1	XM_011523482.2	c.198+22284A>G		intron_variant	Intron 1 of 5		XP_011521784.1
N4BP1	XR_007064930.1	n.406+22284A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
N4BP1	ENST00000262384.4	c.198+22284A>G		intron_variant	Intron 1 of 6	1	NM_153029.4	ENSP00000262384.3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61644 AN: 151948 Hom.: 13518 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61711 AN: 152068 Hom.: 13538 Cov.: 33 AF XY: 0.409 AC XY: 30429 AN XY: 74344

African (AFR) AF: 0.572 AC: 23714 AN: 41462

American (AMR) AF: 0.423 AC: 6468 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3466

East Asian (EAS) AF: 0.248 AC: 1281 AN: 5174

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4820

European-Finnish (FIN) AF: 0.415 AC: 4373 AN: 10548

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

European-Non Finnish (NFE) AF: 0.318 AC: 21639 AN: 67988

Other (OTH) AF: 0.402 AC: 848 AN: 2112

Alfa AF: 0.360 Hom.: 17055

Bravo AF: 0.415

Asia WGS AF: 0.403 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.63
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: rs6500395; hg19: chr16-48621402;