rs11630780

Positions:

• chr15-55836247-A-C
• chr15-55836247-A-G

Variant summary

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

The NM_006154.4(NEDD4):​c.2262+1542T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,652 control chromosomes in the GnomAD database, including 12,485 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 (12485 hom., cov: 30)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4	NM_006154.4	c.2262+1542T>G		intron_variant		ENST00000435532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4	ENST00000435532.8	c.2262+1542T>G		intron_variant		1	NM_006154.4	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60937 AN: 151534 Hom.: 12487 Cov.: 30

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.402 AC: 60960 AN: 151652 Hom.: 12485 Cov.: 30 AF XY: 0.402 AC XY: 29775 AN XY: 74070

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.373

Alfa AF: 0.367 Hom.: 2391

Bravo AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.49

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: rs11630780; hg19: chr15-56128445;