ENST00000508342.5:c.1047G>A

Variant names:

• chr15-55915785-C-T
• rs7174459
• ENST00000508342.5:c.1047G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000508342.5(NEDD4):​c.1047G>A​(p.Ser349Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,154 control chromosomes in the GnomAD database, including 60,512 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 0.24 (4889 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55623 hom.)
• Consequence: NEDD4 ENST00000508342.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508342.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	NM_006154.4	MANE Select	c.291+8861G>A		intron	N/A	NP_006145.2	P46934-4
	NEDD4	NM_001284338.2		c.1047G>A	p.Ser349Ser	synonymous	Exon 1 of 25	NP_001271267.1	P46934-1
	NEDD4	NM_001284339.1		c.1047G>A	p.Ser349Ser	synonymous	Exon 1 of 25	NP_001271268.1	P46934-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000508342.5	TSL:1	c.1047G>A	p.Ser349Ser	synonymous	Exon 1 of 25	ENSP00000424827.1	P46934-1
	NEDD4	ENST00000506154.1	TSL:1	c.1047G>A	p.Ser349Ser	synonymous	Exon 1 of 25	ENSP00000422705.1	P46934-2
	NEDD4	ENST00000338963.6	TSL:1	c.1047G>A	p.Ser349Ser	synonymous	Exon 1 of 22	ENSP00000345530.2	P46934-3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36488 AN: 151874 Hom.: 4881 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.264 AC: 65900 AN: 249958 AF XY: 0.259

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.271 AC: 396051 AN: 1461162 Hom.: 55623 Cov.: 49 AF XY: 0.268 AC XY: 195147 AN XY: 726812

African (AFR) AF: 0.120 AC: 4010 AN: 33468

American (AMR) AF: 0.337 AC: 15057 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 9617 AN: 26102

East Asian (EAS) AF: 0.138 AC: 5494 AN: 39684

South Asian (SAS) AF: 0.170 AC: 14690 AN: 86200

European-Finnish (FIN) AF: 0.324 AC: 17242 AN: 53292

Middle Eastern (MID) AF: 0.215 AC: 1242 AN: 5766

European-Non Finnish (NFE) AF: 0.282 AC: 312953 AN: 1111582

Other (OTH) AF: 0.261 AC: 15746 AN: 60370

GnomAD4 genome AF: 0.240 AC: 36521 AN: 151992 Hom.: 4889 Cov.: 32 AF XY: 0.241 AC XY: 17893 AN XY: 74270

African (AFR) AF: 0.134 AC: 5543 AN: 41472

American (AMR) AF: 0.306 AC: 4668 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1270 AN: 3462

East Asian (EAS) AF: 0.126 AC: 654 AN: 5172

South Asian (SAS) AF: 0.166 AC: 798 AN: 4812

European-Finnish (FIN) AF: 0.327 AC: 3449 AN: 10542

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19388 AN: 67946

Other (OTH) AF: 0.240 AC: 508 AN: 2114

Alfa AF: 0.275 Hom.: 11346

Bravo AF: 0.235

Asia WGS AF: 0.178 AC: 618 AN: 3478

EpiCase AF: 0.283

EpiControl AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.027
DANN	Benign	0.53
PhyloP100		-1.6
PromoterAI		-0.015	Neutral
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: rs7174459; hg19: chr15-56207983; COSMIC: COSV59062369; COSMIC: COSV59062369;