Genetic Variant UBE2I:c.*469T>G (chr16-1325262-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003345.5(UBE2I):c.*469T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 161,480 control chromosomes in the GnomAD database, including 68,110 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 0.92 ( 64310 hom., cov: 33)

Exomes 𝑓: 0.91 ( 3800 hom. )

Consequence

UBE2I
NM_003345.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

24 publications found

Variant links:

Genes affected

UBE2I (HGNC:12485): (ubiquitin conjugating enzyme E2 I) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Four alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

UBE2I links:

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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=-0.65).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UBE2I	NM_003345.5 link	c.*469T>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000397514.8	NP_003336.1
UBE2I	NM_194259.3 link	c.*469T>G	3_prime_UTR_variant	Exon 8 of 8		NP_919235.1
UBE2I	NM_194260.3 link	c.*469T>G	3_prime_UTR_variant	Exon 7 of 7		NP_919236.1
UBE2I	NM_194261.3 link	c.*469T>G	3_prime_UTR_variant	Exon 7 of 7		NP_919237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2I	ENST00000397514.8 link	c.*469T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_003345.5	ENSP00000380649.3		P63279

Frequencies

GnomAD3 genomes

AF:

0.918

AC:

139716

AN:

152190

Hom.:

64246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.965

Gnomad AMI

AF:

0.883

Gnomad AMR

AF:

0.930

Gnomad ASJ

AF:

0.885

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.942

Gnomad FIN

AF:

0.914

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.931

GnomAD4 exome

AF:

0.908

AC:

8329

AN:

9172

Hom.:

3800

Cov.:

AF XY:

0.914

AC XY:

4488

AN XY:

4912

show subpopulations

African (AFR)

AF:

0.983

AC:

AN:

American (AMR)

AF:

0.957

AC:

1301

AN:

1360

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

218

AN:

218

South Asian (SAS)

AF:

0.942

AC:

1042

AN:

1106

European-Finnish (FIN)

AF:

0.926

AC:

1529

AN:

1652

Middle Eastern (MID)

AF:

0.944

AC:

AN:

European-Non Finnish (NFE)

AF:

0.874

AC:

3779

AN:

4324

Other (OTH)

AF:

0.890

AC:

317

AN:

356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.918

AC:

139839

AN:

152308

Hom.:

64310

Cov.:

AF XY:

0.921

AC XY:

68585

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.965

AC:

40109

AN:

41568

American (AMR)

AF:

0.930

AC:

14228

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.885

AC:

3073

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5177

AN:

5180

South Asian (SAS)

AF:

0.941

AC:

4535

AN:

4818

European-Finnish (FIN)

AF:

0.914

AC:

9710

AN:

10618

Middle Eastern (MID)

AF:

0.946

AC:

278

AN:

294

European-Non Finnish (NFE)

AF:

0.881

AC:

59953

AN:

68032

Other (OTH)

AF:

0.931

AC:

1971

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

605

1210

1814

2419

3024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.895

Hom.:

96120

Bravo

AF:

0.922

Asia WGS

AF:

0.975

AC:

3390

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.2

(source)

DANN

Benign

0.40

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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