rs8024944

Positions:

• chr15-55832937-C-A
• chr15-55832937-C-T

Variant summary

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

The ENST00000435532.8(NEDD4):​c.2527+71G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,010,904 control chromosomes in the GnomAD database, including 56,698 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 0.33 (8340 hom., cov: 32)
  • Exomes 𝑓: 0.33 (48358 hom.)
• Consequence: NEDD4 ENST00000435532.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738

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=-0.94).
• 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	Protein	UniProt
NEDD4	NM_006154.4	c.2527+71G>T		intron_variant		ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.2527+71G>T		intron_variant		1	NM_006154.4	ENSP00000410613	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49848 AN: 151770 Hom.: 8342 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.332 AC: 285515 AN: 859016 Hom.: 48358 AF XY: 0.335 AC XY: 148500 AN XY: 443556

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.328 AC: 49858 AN: 151888 Hom.: 8340 Cov.: 32 AF XY: 0.330 AC XY: 24471 AN XY: 74202

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.305

Alfa AF: 0.223 Hom.: 589

Bravo AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.45

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: rs8024944; hg19: chr15-56125135; COSMIC: COSV59059864;