rs8026172

Positions:

• chr15-55832984-T-A

Variant summary

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

The NM_006154.4(NEDD4):​c.2527+24A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,513,316 control chromosomes in the GnomAD database, including 84,368 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 (8335 hom., cov: 32)
  • Exomes 𝑓: 0.33 (76033 hom.)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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=-0.65).
• 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+24A>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+24A>T		intron_variant		1	NM_006154.4	ENSP00000410613	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49840 AN: 151918 Hom.: 8337 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.306

GnomAD3 exomes AF: 0.334 AC: 79592 AN: 237944 Hom.: 13639 AF XY: 0.337 AC XY: 43454 AN XY: 129064

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.257

Gnomad EAS exome AF: 0.294

Gnomad SAS exome AF: 0.432

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.331 AC: 450999 AN: 1361280 Hom.: 76033 Cov.: 19 AF XY: 0.333 AC XY: 227254 AN XY: 681424

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.328 AC: 49850 AN: 152036 Hom.: 8335 Cov.: 32 AF XY: 0.329 AC XY: 24461 AN XY: 74306

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.305

Alfa AF: 0.322 Hom.: 1477

Bravo AF: 0.324

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.6
DANN	Benign	0.90

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: rs8026172; hg19: chr15-56125182; COSMIC: COSV59059874;