dbSNP rs2293983: UBR5:c.4589+114C>T (chr8-102293491-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015902.6(UBR5):c.4589+114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,298,946 control chromosomes in the GnomAD database, including 3,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.051 ( 583 hom., cov: 32)

Exomes 𝑓: 0.036 ( 3283 hom. )

Consequence

UBR5
NM_015902.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.779

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics

UBR5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR5	NM_015902.6 link	c.4589+114C>T		intron_variant	Intron 34 of 58	ENST00000520539.6	NP_056986.2	O95071-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBR5	ENST00000520539.6 link	c.4589+114C>T	intron_variant	Intron 34 of 58	1	NM_015902.6	ENSP00000429084.1	O95071-1
UBR5	ENST00000220959.8 link	c.4589+114C>T	intron_variant	Intron 34 of 58	1		ENSP00000220959.4	O95071-2
UBR5	ENST00000521922.5 link	c.4571+114C>T	intron_variant	Intron 34 of 58	5		ENSP00000427819.1	E7EMW7
UBR5	ENST00000519528.1 link	n.105+114C>T	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7746

AN:

152130

Hom.:

578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0918

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.0670

Gnomad FIN

AF:

0.0633

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0556

GnomAD4 exome

AF:

0.0356

AC:

40802

AN:

1146698

Hom.:

3283

AF XY:

0.0360

AC XY:

20415

AN XY:

567866

show subpopulations

African (AFR)

AF:

0.0454

AC:

1190

AN:

26212

American (AMR)

AF:

0.104

AC:

2577

AN:

24756

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

806

AN:

18284

East Asian (EAS)

AF:

0.368

AC:

13595

AN:

36954

South Asian (SAS)

AF:

0.0644

AC:

3855

AN:

59880

European-Finnish (FIN)

AF:

0.0517

AC:

2245

AN:

43452

Middle Eastern (MID)

AF:

0.0363

AC:

170

AN:

4682

European-Non Finnish (NFE)

AF:

0.0158

AC:

13993

AN:

883848

Other (OTH)

AF:

0.0488

AC:

2371

AN:

48630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1652

3303

4955

6606

8258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0511

AC:

7774

AN:

152248

Hom.:

583

Cov.:

AF XY:

0.0568

AC XY:

4225

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0428

AC:

1780

AN:

41564

American (AMR)

AF:

0.0922

AC:

1409

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0470

AC:

163

AN:

3470

East Asian (EAS)

AF:

0.383

AC:

1983

AN:

5182

South Asian (SAS)

AF:

0.0675

AC:

326

AN:

4830

European-Finnish (FIN)

AF:

0.0633

AC:

670

AN:

10592

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0193

AC:

1311

AN:

68020

Other (OTH)

AF:

0.0583

AC:

123

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

351

701

1052

1402

1753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0345

Hom.:

403

Bravo

AF:

0.0556

Asia WGS

AF:

0.202

AC:

700

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.18

(source)

DANN

Benign

0.71

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over