NM_006154.4:c.1608+740G>A

Variant names:

• chr15-55846229-C-T
• rs8033275
• NM_006154.4:c.1608+740G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006154.4(NEDD4):​c.1608+740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,094 control chromosomes in the GnomAD database, including 39,069 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 0.71 (39069 hom., cov: 33)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.1608+740G>A		intron_variant	Intron 18 of 28	ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.1608+740G>A		intron_variant	Intron 18 of 28	1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108302 AN: 151974 Hom.: 39060 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.712 AC: 108364 AN: 152094 Hom.: 39069 Cov.: 33 AF XY: 0.710 AC XY: 52797 AN XY: 74334

African (AFR) AF: 0.611 AC: 25336 AN: 41474

American (AMR) AF: 0.682 AC: 10424 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2761 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3094 AN: 5172

South Asian (SAS) AF: 0.749 AC: 3614 AN: 4822

European-Finnish (FIN) AF: 0.714 AC: 7539 AN: 10566

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53208 AN: 67984

Other (OTH) AF: 0.689 AC: 1454 AN: 2110

Alfa AF: 0.747 Hom.: 6274

Bravo AF: 0.701

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8033275; hg19: chr15-56138427;