rs12232351

chr15-55848797-T-Achr15-55848797-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.1428+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,608,450 control chromosomes in the GnomAD database, including 88,007 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 0.31 (7515 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80492 hom.)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4	NM_006154.4	c.1428+9A>T		intron_variant		ENST00000435532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4	ENST00000435532.8	c.1428+9A>T		intron_variant		1	NM_006154.4	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47310 AN: 151936 Hom.: 7522 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.330 AC: 82578 AN: 250598 Hom.: 14001 AF XY: 0.334 AC XY: 45186 AN XY: 135472

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.275

Gnomad SAS exome AF: 0.438

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.330 AC: 479999 AN: 1456394 Hom.: 80492 Cov.: 30 AF XY: 0.332 AC XY: 240758 AN XY: 724754

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.311 AC: 47308 AN: 152056 Hom.: 7515 Cov.: 32 AF XY: 0.313 AC XY: 23258 AN XY: 74302

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.296

Alfa AF: 0.319 Hom.: 2585

Bravo AF: 0.305

Asia WGS AF: 0.365 AC: 1269 AN: 3468

EpiCase AF: 0.318

EpiControl AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.90
Dann	Benign	0.71

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: rs12232351; hg19: chr15-56140995; COSMIC: COSV59059882;