Variant chr8-86402014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007013.4(WWP1):c.540-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,549,278 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

WWP1
NM_007013.4 splice_region, intron

Scores

Splicing: ADA: 0.01994

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.199

Variant links:

Genes affected

WWP1 (HGNC:17004): (WW domain containing E3 ubiquitin protein ligase 1) WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008]

WWP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 8-86402014-T-C is Benign according to our data. Variant chr8-86402014-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658677.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWP1	NM_007013.4 link	c.540-5T>C		splice_region_variant, intron_variant		ENST00000517970.6	NP_008944.1	Q9H0M0-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
WWP1	ENST00000517970.6 link	c.540-5T>C	splice_region_variant, intron_variant	1	NM_007013.4	ENSP00000427793.1	Q9H0M0-1
WWP1	ENST00000265428.4 link	c.540-5T>C	splice_region_variant, intron_variant	1		ENSP00000265428.4	Q9H0M0-1
WWP1	ENST00000518683.5 link	n.378+3376T>C	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00236

AC:

511

AN:

216168

Hom.:

AF XY:

0.00234

AC XY:

276

AN XY:

117902

show subpopulations

Gnomad AFR exome

AF:

0.000218

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00341

GnomAD4 exome

AF:

0.00127

AC:

1780

AN:

1396962

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

931

AN XY:

693158

show subpopulations

Gnomad4 AFR exome

AF:

0.0000651

Gnomad4 AMR exome

AF:

0.000238

Gnomad4 ASJ exome

AF:

0.0000833

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000525

Gnomad4 FIN exome

AF:

0.00966

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152316

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.00265

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00104

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

WWP1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.9

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.020

dbscSNV1_RF

Benign

0.056

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over