rs7162435

Variant names:

• chr15-55829136-T-C
• rs7162435
• NM_006154.4:c.*761A>G

Variant summary

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

The NM_001284338.2(NEDD4):​c.*761A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,422 control chromosomes in the GnomAD database, including 8,982 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 0.34 (8967 hom., cov: 33)
  • Exomes 𝑓: 0.33 (15 hom.)
• Consequence: NEDD4 NM_001284338.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 15 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284338.2. 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.*761A>G		3_prime_UTR	Exon 29 of 29	NP_006145.2
	NEDD4	NM_001284338.2		c.*761A>G		3_prime_UTR	Exon 25 of 25	NP_001271267.1
	NEDD4	NM_001284339.1		c.*761A>G		3_prime_UTR	Exon 25 of 25	NP_001271268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000435532.8	TSL:1 MANE Select	c.*761A>G		3_prime_UTR	Exon 29 of 29	ENSP00000410613.3
	NEDD4	ENST00000508342.5	TSL:1	c.*761A>G		3_prime_UTR	Exon 25 of 25	ENSP00000424827.1
	NEDD4	ENST00000506154.1	TSL:1	c.*761A>G		3_prime_UTR	Exon 25 of 25	ENSP00000422705.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51626 AN: 151988 Hom.: 8966 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.331 AC: 104 AN: 314 Hom.: 15 Cov.: 0 AF XY: 0.311 AC XY: 61 AN XY: 196

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: 0.328 AC: 101 AN: 308

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.340 AC: 51650 AN: 152108 Hom.: 8967 Cov.: 33 AF XY: 0.341 AC XY: 25333 AN XY: 74364

African (AFR) AF: 0.376 AC: 15594 AN: 41498

American (AMR) AF: 0.329 AC: 5032 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1675 AN: 5176

South Asian (SAS) AF: 0.426 AC: 2056 AN: 4822

European-Finnish (FIN) AF: 0.303 AC: 3204 AN: 10572

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22124 AN: 67978

Other (OTH) AF: 0.315 AC: 665 AN: 2112

Alfa AF: 0.324 Hom.: 10730

Bravo AF: 0.337

Asia WGS AF: 0.372 AC: 1296 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.063
DANN	Benign	0.19
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7162435; hg19: chr15-56121334;