chr15-55827934-G-C

Variant names:

• chr15-55827934-G-C
• rs11550869
• ENST00000503468.5:n.*4123C>G

Variant summary

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

The ENST00000503468.5(NEDD4):​n.*4123C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,048 control chromosomes in the GnomAD database, including 714 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 0.092 (714 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: NEDD4 ENST00000503468.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4	c.*1963C>G		3_prime_UTR_variant	Exon 29 of 29	ENST00000435532.8	NP_006145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8	c.*1963C>G		3_prime_UTR_variant	Exon 29 of 29	1	NM_006154.4	ENSP00000410613.3

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14034 AN: 151924 Hom.: 714 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0924 AC: 14044 AN: 152042 Hom.: 714 Cov.: 32 AF XY: 0.0919 AC XY: 6831 AN XY: 74338

African (AFR) AF: 0.0631 AC: 2620 AN: 41490

American (AMR) AF: 0.102 AC: 1564 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3468

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5166

South Asian (SAS) AF: 0.0562 AC: 270 AN: 4808

European-Finnish (FIN) AF: 0.0765 AC: 807 AN: 10546

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7422 AN: 67978

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.100 Hom.: 98

Bravo AF: 0.0933

Asia WGS AF: 0.0580 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-1.4
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: rs11550869; hg19: chr15-56120132;