15-55827379-C-T

Variant names:

• chr15-55827379-C-T
• rs3088077
• ENST00000503468.5:n.*4678G>A

Variant summary

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

The ENST00000503468.5(NEDD4):​n.*4678G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,104 control chromosomes in the GnomAD database, including 3,387 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 0.20 (3387 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: NEDD4 ENST00000503468.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.*2518G>A		3_prime_UTR_variant	Exon 29 of 29	ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.*2518G>A		3_prime_UTR_variant	Exon 29 of 29	1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30928 AN: 151968 Hom.: 3392 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.111 AC: 2 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.203 AC: 30929 AN: 152086 Hom.: 3387 Cov.: 32 AF XY: 0.205 AC XY: 15259 AN XY: 74330

African (AFR) AF: 0.112 AC: 4667 AN: 41510

American (AMR) AF: 0.232 AC: 3549 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1726 AN: 5160

South Asian (SAS) AF: 0.223 AC: 1071 AN: 4808

European-Finnish (FIN) AF: 0.214 AC: 2261 AN: 10548

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16055 AN: 67978

Other (OTH) AF: 0.239 AC: 505 AN: 2110

Alfa AF: 0.228 Hom.: 3873

Bravo AF: 0.202

Asia WGS AF: 0.268 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.30
PhyloP100		-1.4
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: rs3088077; hg19: chr15-56119577;