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GeneBe

8-102262068-G-C

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.Val2563=) 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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.77 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1073 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBR5NM_015902.6 linkuse as main transcriptc.7689C>G p.Val2563= splice_region_variant, synonymous_variant 55/59 ENST00000520539.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBR5ENST00000520539.6 linkuse as main transcriptc.7689C>G p.Val2563= splice_region_variant, synonymous_variant 55/591 NM_015902.6 P5O95071-1
UBR5ENST00000220959.8 linkuse as main transcriptc.7686C>G p.Val2562= splice_region_variant, synonymous_variant 55/591 A1O95071-2
UBR5ENST00000521922.5 linkuse as main transcriptc.7668C>G p.Val2556= splice_region_variant, synonymous_variant 55/595 A1
UBR5ENST00000518205.5 linkuse as main transcriptc.873C>G p.Val291= splice_region_variant, synonymous_variant 8/125

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00706
AC:
1073
AN:
152052
Hom.:
11
Cov.:
32
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.:
14
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.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00704
AC:
1072
AN:
152170
Hom.:
11
Cov.:
32
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.:
5
Bravo
AF:
0.00695
Asia WGS
AF:
0.00375
AC:
13
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023UBR5: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
11
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.

Other links and lift over

dbSNP: rs34261575; hg19: chr8-103274296; API