rs12899701

Positions:

• chr15-55829156-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006154.4(NEDD4):​c.*741T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 152,520 control chromosomes in the GnomAD database, including 439 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 0.068 (439 hom., cov: 33)
  • Exomes 𝑓: 0.082 (0 hom.)
• Consequence: NEDD4 NM_006154.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

Genes affected

NEDD4 (HGNC:7727): (NEDD4 E3 ubiquitin protein ligase) This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.*741T>G		3_prime_UTR_variant	29/29	ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.*741T>G		3_prime_UTR_variant	29/29	1	NM_006154.4	ENSP00000410613	P1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10281 AN: 152206 Hom.: 439 Cov.: 33

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0857

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0816 AC: 16 AN: 196 Hom.: 0 Cov.: 0 AF XY: 0.0763 AC XY: 9 AN XY: 118

Gnomad4 FIN exome AF: 0.0781

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0675 AC: 10284 AN: 152324 Hom.: 439 Cov.: 33 AF XY: 0.0659 AC XY: 4907 AN XY: 74496

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.0857

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0516

Gnomad4 FIN AF: 0.0800

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0868 Hom.: 249

Bravo AF: 0.0634

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.80

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: rs12899701; hg19: chr15-56121354;