rs8026172

Variant names:

• chr15-55832984-T-A
• rs8026172
• NM_006154.4:c.2527+24A>T

Variant summary

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

The NM_006154.4(NEDD4):​c.2527+24A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,513,316 control chromosomes in the GnomAD database, including 84,368 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 0.33 (8335 hom., cov: 32)
  • Exomes 𝑓: 0.33 (76033 hom.)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 9 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=-0.65).
• 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_006154.4. 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.2527+24A>T		intron	N/A	NP_006145.2
	NEDD4	NM_001284338.2		c.3784+24A>T		intron	N/A	NP_001271267.1
	NEDD4	NM_001284339.1		c.3736+24A>T		intron	N/A	NP_001271268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000435532.8	TSL:1 MANE Select	c.2527+24A>T		intron	N/A	ENSP00000410613.3
	NEDD4	ENST00000508342.5	TSL:1	c.3784+24A>T		intron	N/A	ENSP00000424827.1
	NEDD4	ENST00000506154.1	TSL:1	c.3736+24A>T		intron	N/A	ENSP00000422705.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49840 AN: 151918 Hom.: 8337 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.334 AC: 79592 AN: 237944 AF XY: 0.337

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.257

Gnomad EAS exome AF: 0.294

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.331 AC: 450999 AN: 1361280 Hom.: 76033 Cov.: 19 AF XY: 0.333 AC XY: 227254 AN XY: 681424

African (AFR) AF: 0.341 AC: 10534 AN: 30862

American (AMR) AF: 0.341 AC: 13612 AN: 39900

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6387 AN: 24724

East Asian (EAS) AF: 0.338 AC: 13200 AN: 39110

South Asian (SAS) AF: 0.425 AC: 34699 AN: 81616

European-Finnish (FIN) AF: 0.311 AC: 16377 AN: 52722

Middle Eastern (MID) AF: 0.323 AC: 1777 AN: 5506

European-Non Finnish (NFE) AF: 0.326 AC: 336070 AN: 1029936

Other (OTH) AF: 0.322 AC: 18343 AN: 56904

GnomAD4 genome AF: 0.328 AC: 49850 AN: 152036 Hom.: 8335 Cov.: 32 AF XY: 0.329 AC XY: 24461 AN XY: 74306

African (AFR) AF: 0.335 AC: 13879 AN: 41430

American (AMR) AF: 0.326 AC: 4985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1672 AN: 5162

South Asian (SAS) AF: 0.426 AC: 2054 AN: 4820

European-Finnish (FIN) AF: 0.304 AC: 3208 AN: 10568

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.325 AC: 22110 AN: 67988

Other (OTH) AF: 0.305 AC: 645 AN: 2112

Alfa AF: 0.322 Hom.: 1477

Bravo AF: 0.324

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.6
DANN	Benign	0.90
PhyloP100		-0.55
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: rs8026172; hg19: chr15-56125182; COSMIC: COSV59059874;