Variant 8-102270190-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015902.6(UBR5):c.7086-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 1,609,624 control chromosomes in the GnomAD database, including 576 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.036 ( 297 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 279 hom. )

Consequence

UBR5
NM_015902.6 splice_region, intron

Scores

Splicing: ADA: 0.005986

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.657

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-102270190-G-T is Benign according to our data. Variant chr8-102270190-G-T is described in ClinVar as [Benign]. Clinvar id is 3055803.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR5	NM_015902.6 link	c.7086-7C>A		splice_region_variant, intron_variant		ENST00000520539.6	NP_056986.2	O95071-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
UBR5	ENST00000520539.6 link	c.7086-7C>A	splice_region_variant, intron_variant	1	NM_015902.6	ENSP00000429084.1	O95071-1
UBR5	ENST00000220959.8 link	c.7086-7C>A	splice_region_variant, intron_variant	1		ENSP00000220959.4	O95071-2
UBR5	ENST00000521922.5 link	c.7068-7C>A	splice_region_variant, intron_variant	5		ENSP00000427819.1	E7EMW7
UBR5	ENST00000518205.5 link	c.273-7C>A	splice_region_variant, intron_variant	5		ENSP00000428693.1	E7ET84

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5485

AN:

152146

Hom.:

297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.0377

GnomAD3 exomes

AF:

0.0101

AC:

2492

AN:

247904

Hom.:

121

AF XY:

0.00772

AC XY:

1034

AN XY:

133944

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.000407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000466

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000829

Gnomad OTH exome

AF:

0.00563

GnomAD4 exome

AF:

0.00403

AC:

5877

AN:

1457360

Hom.:

279

Cov.:

AF XY:

0.00356

AC XY:

2579

AN XY:

724478

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000338

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000464

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0362

AC:

5508

AN:

152264

Hom.:

297

Cov.:

AF XY:

0.0348

AC XY:

2587

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.0373

Alfa

AF:

0.00935

Hom.:

Bravo

AF:

0.0410

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00101

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

-0.81

CADD

Benign

6.8

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0060

dbscSNV1_RF

Benign

0.084

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