Menu
GeneBe

15-55834113-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_006154.4(NEDD4):c.2355G>A(p.Val785=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,613,596 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 43 hom. )

Consequence

NEDD4
NM_006154.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.221
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-55834113-C-T is Benign according to our data. Variant chr15-55834113-C-T is described in ClinVar as [Benign]. Clinvar id is 721693.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.221 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00215 (3145/1461344) while in subpopulation SAS AF= 0.0165 (1419/86238). AF 95% confidence interval is 0.0157. There are 43 homozygotes in gnomad4_exome. There are 1937 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEDD4NM_006154.4 linkuse as main transcriptc.2355G>A p.Val785= synonymous_variant 26/29 ENST00000435532.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEDD4ENST00000435532.8 linkuse as main transcriptc.2355G>A p.Val785= synonymous_variant 26/291 NM_006154.4 P1P46934-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00198
AC:
301
AN:
152134
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0149
Gnomad FIN
AF:
0.00925
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00175
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00350
AC:
879
AN:
251080
Hom.:
9
AF XY:
0.00416
AC XY:
565
AN XY:
135738
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.000695
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0163
Gnomad FIN exome
AF:
0.00786
Gnomad NFE exome
AF:
0.00166
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00215
AC:
3145
AN:
1461344
Hom.:
43
Cov.:
31
AF XY:
0.00266
AC XY:
1937
AN XY:
727006
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.000842
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0165
Gnomad4 FIN exome
AF:
0.00849
Gnomad4 NFE exome
AF:
0.000972
Gnomad4 OTH exome
AF:
0.00210
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00197
AC:
300
AN:
152252
Hom.:
1
Cov.:
32
AF XY:
0.00258
AC XY:
192
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0149
Gnomad4 FIN
AF:
0.00925
Gnomad4 NFE
AF:
0.00175
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00163
Hom.:
0
Bravo
AF:
0.000740
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.00196
EpiControl
AF:
0.000533

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
8.1
Dann
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140800682; hg19: chr15-56126311; API