rs6500395

Positions:

• chr16-48587491-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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/exons	MANE	UniProt
N4BP1	NM_153029.4	c.198+22284A>G		intron_variant		ENST00000262384.4
N4BP1	XM_011523482.2	c.198+22284A>G		intron_variant
N4BP1	XR_007064930.1	n.406+22284A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
N4BP1	ENST00000262384.4	c.198+22284A>G		intron_variant		1	NM_153029.4	P1
N4BP1	ENST00000564710.1	c.-61+16169A>G		intron_variant		4
N4BP1	ENST00000564124.5	n.301-25047A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.402

Alfa AF: 0.334 Hom.: 7671

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

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: rs6500395; hg19: chr16-48621402;