15-55871094-T-G

Variant names:

• chr15-55871094-T-G
• rs1912405
• NM_006154.4:c.404+1321A>C

Variant summary

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

The NM_006154.4(NEDD4):​c.404+1321A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,996 control chromosomes in the GnomAD database, including 39,975 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 0.72 (39975 hom., cov: 32)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.404+1321A>C		intron_variant	Intron 7 of 28	ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.404+1321A>C		intron_variant	Intron 7 of 28	1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109422 AN: 151878 Hom.: 39959 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109497 AN: 151996 Hom.: 39975 Cov.: 32 AF XY: 0.717 AC XY: 53271 AN XY: 74264

African (AFR) AF: 0.613 AC: 25391 AN: 41446

American (AMR) AF: 0.687 AC: 10479 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2781 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3080 AN: 5148

South Asian (SAS) AF: 0.757 AC: 3651 AN: 4822

European-Finnish (FIN) AF: 0.712 AC: 7510 AN: 10544

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54156 AN: 67992

Other (OTH) AF: 0.697 AC: 1471 AN: 2110

Alfa AF: 0.775 Hom.: 20693

Bravo AF: 0.709

Asia WGS AF: 0.673 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.41
PhyloP100		-1.3
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: rs1912405; hg19: chr15-56163292;