Variant 3-39065870-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_001346227.2(WDR48):c.-147C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,600,396 control chromosomes in the GnomAD database, including 2,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.069 ( 1174 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 946 hom. )

Consequence

WDR48
NM_001346227.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00700

Variant links:

Genes affected

WDR48 (HGNC:30914): (WD repeat domain 48) The protein encoded by this gene has been shown to interact with ubiquitin specific peptidase 1 (USP1), activating the deubiquitinating activity of USP1 and allowing it to remove the ubiquitin moiety from monoubiquitinated FANCD2. FANCD2 is ubiquitinated in response to DNA damage. [provided by RefSeq, Sep 2016]

WDR48 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-39065870-C-G is Benign according to our data. Variant chr3-39065870-C-G is described in ClinVar as [Benign]. Clinvar id is 3060884.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR48	NM_020839.4 link	c.249C>G	p.Leu83Leu	synonymous_variant	Exon 3 of 19	ENST00000302313.10	NP_065890.1	Q8TAF3-1A0A024R2L1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR48	ENST00000302313.10 link	c.249C>G	p.Leu83Leu	synonymous_variant	Exon 3 of 19	1	NM_020839.4	ENSP00000307491.5		Q8TAF3-1

Frequencies

GnomAD3 genomes

AF:

0.0693

AC:

10543

AN:

152086

Hom.:

1173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0180

AC:

4317

AN:

239638

Hom.:

403

AF XY:

0.0133

AC XY:

1725

AN XY:

129664

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.00439

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000573

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00762

AC:

11037

AN:

1448192

Hom.:

946

Cov.:

AF XY:

0.00670

AC XY:

4827

AN XY:

720214

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.00484

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

AF:

0.0695

AC:

10576

AN:

152204

Hom.:

1174

Cov.:

AF XY:

0.0680

AC XY:

5060

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0203

Hom.:

Bravo

AF:

0.0803

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

WDR48-related disorder

Benign:1

Jun 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.8

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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