rs12908466

Positions:

• chr15-55833864-T-C

Variant summary

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

The NM_006154.4(NEDD4):​c.2430+174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,248 control chromosomes in the GnomAD database, including 471 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 0.073 (471 hom., cov: 32)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4	NM_006154.4	c.2430+174A>G		intron_variant		ENST00000435532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4	ENST00000435532.8	c.2430+174A>G		intron_variant		1	NM_006154.4	P1

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11135 AN: 152130 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0857

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.0642

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

GnomAD4 genome AF: 0.0732 AC: 11142 AN: 152248 Hom.: 471 Cov.: 32 AF XY: 0.0718 AC XY: 5343 AN XY: 74452

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0857

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0801

Gnomad4 NFE AF: 0.0993

Gnomad4 OTH AF: 0.0636

Alfa AF: 0.0899 Hom.: 98

Bravo AF: 0.0696

Asia WGS AF: 0.0440 AC: 152 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.077
DANN	Benign	0.52

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: rs12908466; hg19: chr15-56126062;