Variant 11-113808338-C-T 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_001346252.4(USP28):c.2264G>A(p.Arg755His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,613,910 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

USP28
NM_001346252.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.960

Variant links:

Genes affected

USP28 (HGNC:12625): (ubiquitin specific peptidase 28) The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]

USP28 links:

USP28 (HGNC:):

USP28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003255397).

BP6

Variant 11-113808338-C-T is Benign according to our data. Variant chr11-113808338-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2213733.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP28	NM_001346252.4 linkuse as main transcript	c.2264G>A	p.Arg755His	missense_variant	18/26	ENST00000696973.1	NP_001333181.1	A0A8V8TLZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP28	ENST00000696973.1 linkuse as main transcript	c.2264G>A	p.Arg755His	missense_variant	18/26		NM_001346252.4	ENSP00000513009.1		A0A8V8TLZ9

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

210

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00140

AC:

352

AN:

251160

Hom.:

AF XY:

0.00131

AC XY:

178

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000373

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00241

AC:

3527

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1694

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000338

Gnomad4 NFE exome

AF:

0.00295

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00138

AC:

210

AN:

152230

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00125

AC:

152

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.1

DANN

Benign

0.73

DEOGEN2

Benign

0.041

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.12

N;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.79

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.55

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.051

MVP

0.19

MPC

0.22

ClinPred

0.0033

GERP RS

-7.5

Varity_R

0.012

gMVP

0.14

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