Variant 8-102262068-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_015902.6(UBR5):c.7689C>G(p.Val2563Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,583,228 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 11 hom., cov: 32)

Exomes 𝑓: 0.011 ( 114 hom. )

Consequence

UBR5
NM_015902.6 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.77

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 8-102262068-G-C is Benign according to our data. Variant chr8-102262068-G-C is described in ClinVar as [Benign]. Clinvar id is 2658721.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.77 with no splicing effect.

BS2

High AC in GnomAd4 at 1072 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR5	NM_015902.6 link	c.7689C>G	p.Val2563Val	splice_region_variant, synonymous_variant	55/59	ENST00000520539.6	NP_056986.2	O95071-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBR5	ENST00000520539.6 link	c.7689C>G	p.Val2563Val	splice_region_variant, synonymous_variant	55/59	1	NM_015902.6	ENSP00000429084.1	O95071-1
UBR5	ENST00000220959.8 link	c.7686C>G	p.Val2562Val	splice_region_variant, synonymous_variant	55/59	1		ENSP00000220959.4	O95071-2
UBR5	ENST00000521922.5 link	c.7668C>G	p.Val2556Val	splice_region_variant, synonymous_variant	55/59	5		ENSP00000427819.1	E7EMW7
UBR5	ENST00000518205.5 link	c.873C>G	p.Val291Val	splice_region_variant, synonymous_variant	8/12	5		ENSP00000428693.1	E7ET84

Frequencies

GnomAD3 genomes

AF:

0.00706

AC:

1073

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00732

AC:

1650

AN:

225398

Hom.:

AF XY:

0.00741

AC XY:

905

AN XY:

122154

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.00489

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00270

Gnomad FIN exome

AF:

0.00321

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00575

GnomAD4 exome

AF:

0.0112

AC:

16091

AN:

1431058

Hom.:

114

Cov.:

AF XY:

0.0110

AC XY:

7802

AN XY:

710406

show subpopulations

Gnomad4 AFR exome

AF:

0.00202

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00540

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00289

Gnomad4 FIN exome

AF:

0.00382

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.00789

GnomAD4 genome

AF:

0.00704

AC:

1072

AN:

152170

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

486

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00302

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00695

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0102

EpiControl

AF:

0.0106

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

UBR5: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.84

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