rs8028559

Variant names:

• chr15-55838711-A-G
• rs8028559
• NM_006154.4:c.2032-107T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006154.4(NEDD4):​c.2032-107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 671,820 control chromosomes in the GnomAD database, including 48,905 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 0.40 (13037 hom., cov: 33)
  • Exomes 𝑓: 0.37 (35868 hom.)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.2032-107T>C		intron_variant	Intron 21 of 28	ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.2032-107T>C		intron_variant	Intron 21 of 28	1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61436 AN: 151960 Hom.: 13027 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.367 AC: 190966 AN: 519742 Hom.: 35868 AF XY: 0.369 AC XY: 102293 AN XY: 276986

African (AFR) AF: 0.529 AC: 7219 AN: 13638

American (AMR) AF: 0.373 AC: 8087 AN: 21686

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 4410 AN: 15822

East Asian (EAS) AF: 0.346 AC: 10755 AN: 31124

South Asian (SAS) AF: 0.431 AC: 21530 AN: 49944

European-Finnish (FIN) AF: 0.351 AC: 11852 AN: 33764

Middle Eastern (MID) AF: 0.338 AC: 773 AN: 2290

European-Non Finnish (NFE) AF: 0.359 AC: 116162 AN: 323262

Other (OTH) AF: 0.361 AC: 10178 AN: 28212

GnomAD4 genome AF: 0.404 AC: 61480 AN: 152078 Hom.: 13037 Cov.: 33 AF XY: 0.402 AC XY: 29897 AN XY: 74338

African (AFR) AF: 0.519 AC: 21525 AN: 41452

American (AMR) AF: 0.381 AC: 5821 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5168

South Asian (SAS) AF: 0.434 AC: 2091 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3630 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24565 AN: 67996

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.387 Hom.: 3293

Bravo AF: 0.408

Asia WGS AF: 0.401 AC: 1397 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8028559; hg19: chr15-56130909; COSMIC: COSV107444576;