chr15-55838711-A-G

Position:

• chr15-55838711-A-G

Variant summary

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

The ENST00000435532.8(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 ENST00000435532.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=-0.83).
• 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/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.2032-107T>C		intron_variant		ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.2032-107T>C		intron_variant		1	NM_006154.4	ENSP00000410613	P1

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

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.361

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

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.370

Alfa AF: 0.397 Hom.: 1989

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

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: rs8028559; hg19: chr15-56130909;