Variant 8-102264525-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015902.6(UBR5):c.7635A>C(p.Leu2545Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,586,512 control chromosomes in the GnomAD database, including 18,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1425 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17266 hom. )

Consequence

UBR5
NM_015902.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.713

Variant links:

Genes affected

UBR5 (HGNC:16806): (ubiquitin protein ligase E3 component n-recognin 5) This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation. [provided by RefSeq, Jul 2008]

UBR5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 8-102264525-T-G is Benign according to our data. Variant chr8-102264525-T-G is described in ClinVar as [Benign]. Clinvar id is 3060589.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.713 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR5	NM_015902.6 link	c.7635A>C	p.Leu2545Leu	synonymous_variant	54/59	ENST00000520539.6	NP_056986.2	O95071-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBR5	ENST00000520539.6 link	c.7635A>C	p.Leu2545Leu	synonymous_variant	54/59	1	NM_015902.6	ENSP00000429084.1	O95071-1
UBR5	ENST00000220959.8 link	c.7632A>C	p.Leu2544Leu	synonymous_variant	54/59	1		ENSP00000220959.4	O95071-2
UBR5	ENST00000521922.5 link	c.7614A>C	p.Leu2538Leu	synonymous_variant	54/59	5		ENSP00000427819.1	E7EMW7
UBR5	ENST00000518205.5 link	c.819A>C	p.Leu273Leu	synonymous_variant	7/12	5		ENSP00000428693.1	E7ET84

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18812

AN:

152088

Hom.:

1425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.00981

Gnomad SAS

AF:

0.0399

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.112

AC:

26093

AN:

233774

Hom.:

1826

AF XY:

0.113

AC XY:

14272

AN XY:

126304

show subpopulations

Gnomad AFR exome

AF:

0.0665

Gnomad AMR exome

AF:

0.0637

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.00876

Gnomad SAS exome

AF:

0.0412

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.147

AC:

211430

AN:

1434306

Hom.:

17266

Cov.:

AF XY:

0.145

AC XY:

103542

AN XY:

713720

show subpopulations

Gnomad4 AFR exome

AF:

0.0637

Gnomad4 AMR exome

AF:

0.0684

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.00974

Gnomad4 SAS exome

AF:

0.0428

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.124

AC:

18805

AN:

152206

Hom.:

1425

Cov.:

AF XY:

0.121

AC XY:

8970

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0709

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.00964

Gnomad4 SAS

AF:

0.0401

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.157

Hom.:

3947

Bravo

AF:

0.118

Asia WGS

AF:

0.0350

AC:

121

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

UBR5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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

-0.71

CADD

Benign

2.5

DANN

Benign

0.71

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