15-55827934-G-C

Position:

• chr15-55827934-G-C

Variant summary

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

The NM_006154.4(NEDD4):​c.*1963C>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 0.0924 in 152,048 control chromosomes in the GnomAD database, including 714 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 0.092 (714 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: NEDD4 NM_006154.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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]

NEDD4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.*1963C>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	c.*1963C>G		3_prime_UTR_variant	29/29	1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14034 AN: 151924 Hom.: 714 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.0924 AC: 14044 AN: 152042 Hom.: 714 Cov.: 32 AF XY: 0.0919 AC XY: 6831 AN XY: 74338

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.102

Alfa AF: 0.100 Hom.: 98

Bravo AF: 0.0933

Asia WGS AF: 0.0580 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.46

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: rs11550869; hg19: chr15-56120132;