rs17819300

chr15-55918731-A-Gchr15-55918731-A-T

Variant summary

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

The NM_006154.4(NEDD4):c.291+5915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,260 control chromosomes in the GnomAD database, including 568 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 0.078 (568 hom., cov: 32)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4	NM_006154.4	c.291+5915T>C		intron_variant		ENST00000435532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4	ENST00000435532.8	c.291+5915T>C		intron_variant		1	NM_006154.4	P1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11818 AN: 152142 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0777 AC: 11823 AN: 152260 Hom.: 568 Cov.: 32 AF XY: 0.0781 AC XY: 5814 AN XY: 74438

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.0935

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0819

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0945 Hom.: 983

Bravo AF: 0.0773

Asia WGS AF: 0.0570 AC: 199 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.2
Dann	Benign	0.24

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: rs17819300; hg19: chr15-56210929;