dbSNP rs12232351: NEDD4:c.1428+9A>T (chr15-55848797-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006154.4(NEDD4):c.1428+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,608,450 control chromosomes in the GnomAD database, including 88,007 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 ( 7515 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80492 hom. )

Consequence

NEDD4
NM_006154.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.753

Publications

16 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4 link	c.1428+9A>T		intron_variant	Intron 15 of 28	ENST00000435532.8	NP_006145.2	P46934-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8 link	c.1428+9A>T		intron_variant	Intron 15 of 28	1	NM_006154.4	ENSP00000410613.3		P46934-4

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47310

AN:

151936

Hom.:

7522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.297

GnomAD2 exomes

AF:

0.330

AC:

82578

AN:

250598

AF XY:

0.334

show subpopulations

Gnomad AFR exome

AF:

0.274

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.330

AC:

479999

AN:

1456394

Hom.:

80492

Cov.:

AF XY:

0.332

AC XY:

240758

AN XY:

724754

show subpopulations

African (AFR)

AF:

0.281

AC:

9378

AN:

33398

American (AMR)

AF:

0.342

AC:

15238

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

6743

AN:

26082

East Asian (EAS)

AF:

0.320

AC:

12668

AN:

39578

South Asian (SAS)

AF:

0.434

AC:

37231

AN:

85804

European-Finnish (FIN)

AF:

0.312

AC:

16627

AN:

53374

Middle Eastern (MID)

AF:

0.321

AC:

1843

AN:

5748

European-Non Finnish (NFE)

AF:

0.326

AC:

361050

AN:

1107666

Other (OTH)

AF:

0.319

AC:

19221

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15344

30687

46031

61374

76718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.311

AC:

47308

AN:

152056

Hom.:

7515

Cov.:

AF XY:

0.313

AC XY:

23258

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.277

AC:

11504

AN:

41490

American (AMR)

AF:

0.321

AC:

4904

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

916

AN:

3472

East Asian (EAS)

AF:

0.306

AC:

1580

AN:

5162

South Asian (SAS)

AF:

0.438

AC:

2106

AN:

4810

European-Finnish (FIN)

AF:

0.303

AC:

3199

AN:

10572

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22091

AN:

67960

Other (OTH)

AF:

0.296

AC:

626

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1689

3379

5068

6758

8447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.319

Hom.:

2585

Bravo

AF:

0.305

Asia WGS

AF:

0.365

AC:

1269

AN:

3468

EpiCase

AF:

0.318

EpiControl

AF:

0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.90

(source)

DANN

Benign

0.71

PhyloP100

-0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs12232351

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over