rs12899701

Variant names:

• chr15-55829156-A-C
• rs12899701
• ENST00000503468.5:n.*2901T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000503468.5(NEDD4):​n.*2901T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 152,520 control chromosomes in the GnomAD database, including 439 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 0.068 (439 hom., cov: 33)
  • Exomes 𝑓: 0.082 (0 hom.)
• Consequence: NEDD4 ENST00000503468.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	NM_006154.4	MANE Select	c.*741T>G		3_prime_UTR	Exon 29 of 29	NP_006145.2
	NEDD4	NR_104302.2		n.4772T>G		non_coding_transcript_exon	Exon 21 of 21
	NEDD4	NM_001284338.2		c.*741T>G		3_prime_UTR	Exon 25 of 25	NP_001271267.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000503468.5	TSL:1	n.*2901T>G		non_coding_transcript_exon	Exon 21 of 21	ENSP00000426051.1
	NEDD4	ENST00000435532.8	TSL:1 MANE Select	c.*741T>G		3_prime_UTR	Exon 29 of 29	ENSP00000410613.3
	NEDD4	ENST00000508342.5	TSL:1	c.*741T>G		3_prime_UTR	Exon 25 of 25	ENSP00000424827.1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10281 AN: 152206 Hom.: 439 Cov.: 33

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0857

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0816 AC: 16 AN: 196 Hom.: 0 Cov.: 0 AF XY: 0.0763 AC XY: 9 AN XY: 118

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0781 AC: 15 AN: 192

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0675 AC: 10284 AN: 152324 Hom.: 439 Cov.: 33 AF XY: 0.0659 AC XY: 4907 AN XY: 74496

African (AFR) AF: 0.0173 AC: 718 AN: 41592

American (AMR) AF: 0.0783 AC: 1197 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 297 AN: 3466

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5190

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4826

European-Finnish (FIN) AF: 0.0800 AC: 849 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6745 AN: 68026

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0751 Hom.: 306

Bravo AF: 0.0634

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.80
PhyloP100		0.11
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: rs12899701; hg19: chr15-56121354;