rs7162435

Positions:

• chr15-55829136-T-C

Variant summary

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

The NM_006154.4(NEDD4):​c.*761A>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 0.34 in 152,422 control chromosomes in the GnomAD database, including 8,982 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 0.34 (8967 hom., cov: 33)
  • Exomes 𝑓: 0.33 (15 hom.)
• Consequence: NEDD4 NM_006154.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4	NM_006154.4	c.*761A>G		3_prime_UTR_variant	29/29	ENST00000435532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4	ENST00000435532.8	c.*761A>G		3_prime_UTR_variant	29/29	1	NM_006154.4	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51626 AN: 151988 Hom.: 8966 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.331 AC: 104 AN: 314 Hom.: 15 Cov.: 0 AF XY: 0.311 AC XY: 61 AN XY: 196

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.340 AC: 51650 AN: 152108 Hom.: 8967 Cov.: 33 AF XY: 0.341 AC XY: 25333 AN XY: 74364

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.315

Alfa AF: 0.321 Hom.: 8149

Bravo AF: 0.337

Asia WGS AF: 0.372 AC: 1296 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.063
DANN	Benign	0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7162435; hg19: chr15-56121334;