15-55902679-T-C

Position:

• chr15-55902679-T-C

Variant summary

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

The ENST00000435532.8(NEDD4):​c.291+21967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,994 control chromosomes in the GnomAD database, including 7,665 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 (7665 hom., cov: 33)
• Consequence: NEDD4 ENST00000435532.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.291+21967A>G		intron_variant		ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.291+21967A>G		intron_variant		1	NM_006154.4	ENSP00000410613	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47807 AN: 151876 Hom.: 7667 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 47822 AN: 151994 Hom.: 7665 Cov.: 33 AF XY: 0.317 AC XY: 23518 AN XY: 74278

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.297

Alfa AF: 0.322 Hom.: 2932

Bravo AF: 0.309

Asia WGS AF: 0.356 AC: 1240 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.65

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: rs8032158; hg19: chr15-56194877;