chr15-55871094-T-G

Position:

• chr15-55871094-T-G

Variant summary

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

The NM_006154.4(NEDD4):​c.404+1321A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,996 control chromosomes in the GnomAD database, including 39,975 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 0.72 (39975 hom., cov: 32)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

NEDD4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.404+1321A>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.404+1321A>C		intron_variant		1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109422 AN: 151878 Hom.: 39959 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.720 AC: 109497 AN: 151996 Hom.: 39975 Cov.: 32 AF XY: 0.717 AC XY: 53271 AN XY: 74264

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.697

Alfa AF: 0.775 Hom.: 18128

Bravo AF: 0.709

Asia WGS AF: 0.673 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.41

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: rs1912405; hg19: chr15-56163292;