15-55838491-T-A

Variant names:

• chr15-55838491-T-A
• rs12906245
• NM_006154.4:c.2127+18A>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.2127+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,541,996 control chromosomes in the GnomAD database, including 6,304 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 0.074 (478 hom., cov: 33)
  • Exomes 𝑓: 0.088 (5826 hom.)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 5 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=-0.71).
• 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: NM_006154.4. 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.2127+18A>T		intron	N/A	NP_006145.2	P46934-4
	NEDD4	NM_001284338.2		c.3384+18A>T		intron	N/A	NP_001271267.1	P46934-1
	NEDD4	NM_001284339.1		c.3336+18A>T		intron	N/A	NP_001271268.1	P46934-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000435532.8	TSL:1 MANE Select	c.2127+18A>T		intron	N/A	ENSP00000410613.3	P46934-4
	NEDD4	ENST00000508342.5	TSL:1	c.3384+18A>T		intron	N/A	ENSP00000424827.1	P46934-1
	NEDD4	ENST00000506154.1	TSL:1	c.3336+18A>T		intron	N/A	ENSP00000422705.1	P46934-2

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11217 AN: 152156 Hom.: 473 Cov.: 33

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.0659

GnomAD2 exomes AF: 0.0762 AC: 19030 AN: 249722 AF XY: 0.0756

Gnomad AFR exome AF: 0.0372

Gnomad AMR exome AF: 0.0730

Gnomad ASJ exome AF: 0.0940

Gnomad EAS exome AF: 0.00359

Gnomad FIN exome AF: 0.0809

Gnomad NFE exome AF: 0.0996

Gnomad OTH exome AF: 0.0753

GnomAD4 exome AF: 0.0875 AC: 121658 AN: 1389722 Hom.: 5826 Cov.: 24 AF XY: 0.0867 AC XY: 60295 AN XY: 695646

African (AFR) AF: 0.0367 AC: 1175 AN: 31994

American (AMR) AF: 0.0725 AC: 3225 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 2405 AN: 25704

East Asian (EAS) AF: 0.00352 AC: 138 AN: 39232

South Asian (SAS) AF: 0.0491 AC: 4162 AN: 84814

European-Finnish (FIN) AF: 0.0829 AC: 4321 AN: 52094

Middle Eastern (MID) AF: 0.0419 AC: 236 AN: 5638

European-Non Finnish (NFE) AF: 0.0968 AC: 101389 AN: 1047784

Other (OTH) AF: 0.0795 AC: 4607 AN: 57964

GnomAD4 genome AF: 0.0738 AC: 11240 AN: 152274 Hom.: 478 Cov.: 33 AF XY: 0.0726 AC XY: 5404 AN XY: 74462

African (AFR) AF: 0.0395 AC: 1641 AN: 41566

American (AMR) AF: 0.0794 AC: 1214 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 297 AN: 3472

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5192

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4828

European-Finnish (FIN) AF: 0.0803 AC: 852 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0992 AC: 6745 AN: 68008

Other (OTH) AF: 0.0652 AC: 138 AN: 2116

Alfa AF: 0.0869 Hom.: 119

Bravo AF: 0.0701

Asia WGS AF: 0.0430 AC: 148 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.27
DANN	Benign	0.70
PhyloP100		-1.6
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: rs12906245; hg19: chr15-56130689;