Genetic Variant UBE2H:c.246-95G>A (chr7-129857658-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003344.4(UBE2H):c.246-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,292,154 control chromosomes in the GnomAD database, including 4,619 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 0.064 ( 372 hom., cov: 32)

Exomes 𝑓: 0.081 ( 4247 hom. )

Consequence

UBE2H
NM_003344.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.160

Publications

2 publications found

Variant links:

Genes affected

UBE2H (HGNC:12484): (ubiquitin conjugating enzyme E2 H) 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. The encoded protein sequence is 100% identical to the mouse homolog and 98% identical to the frog and zebrafish homologs. Three alternatively spliced transcript variants have been found for this gene and they encode distinct isoforms. [provided by RefSeq, Feb 2011]

UBE2H 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE2H	NM_003344.4	MANE Select	c.246-95G>A	intron	N/A	NP_003335.1	P62256-1
UBE2H	NM_182697.3		c.206-18323G>A	intron	N/A	NP_874356.1	P62256-2
UBE2H	NM_001202498.2		c.36-95G>A	intron	N/A	NP_001189427.1	A0A3B3IU20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE2H	ENST00000355621.8	TSL:1 MANE Select	c.246-95G>A	intron	N/A	ENSP00000347836.3	P62256-1
UBE2H	ENST00000473814.6	TSL:1	c.206-18323G>A	intron	N/A	ENSP00000419097.2	P62256-2
UBE2H	ENST00000871229.1		c.246-95G>A	intron	N/A	ENSP00000541288.1

Frequencies

GnomAD3 genomes

AF:

0.0638

AC:

9695

AN:

152004

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.0848

Gnomad AMR

AF:

0.0539

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.0447

Gnomad SAS

AF:

0.0268

Gnomad FIN

AF:

0.0931

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.0915

Gnomad OTH

AF:

0.0635

GnomAD4 exome

AF:

0.0812

AC:

92528

AN:

1140032

Hom.:

4247

AF XY:

0.0795

AC XY:

45921

AN XY:

577482

show subpopulations

African (AFR)

AF:

0.0193

AC:

485

AN:

25066

American (AMR)

AF:

0.0455

AC:

1470

AN:

32298

Ashkenazi Jewish (ASJ)

AF:

0.0255

AC:

546

AN:

21438

East Asian (EAS)

AF:

0.0289

AC:

1069

AN:

36942

South Asian (SAS)

AF:

0.0288

AC:

2013

AN:

69864

European-Finnish (FIN)

AF:

0.0846

AC:

4310

AN:

50960

Middle Eastern (MID)

AF:

0.0423

AC:

193

AN:

4566

European-Non Finnish (NFE)

AF:

0.0930

AC:

79012

AN:

849928

Other (OTH)

AF:

0.0700

AC:

3430

AN:

48970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3964

7928

11893

15857

19821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2570

5140

7710

10280

12850

<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:

0.0638

AC:

9699

AN:

152122

Hom.:

372

Cov.:

AF XY:

0.0630

AC XY:

4685

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0237

AC:

982

AN:

41496

American (AMR)

AF:

0.0538

AC:

822

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3466

East Asian (EAS)

AF:

0.0450

AC:

233

AN:

5182

South Asian (SAS)

AF:

0.0266

AC:

128

AN:

4818

European-Finnish (FIN)

AF:

0.0931

AC:

983

AN:

10554

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0915

AC:

6223

AN:

68006

Other (OTH)

AF:

0.0614

AC:

130

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

485

971

1456

1942

2427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0193

Hom.:

Bravo

AF:

0.0594

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.1

(source)

DANN

Benign

0.52

PhyloP100

-0.16

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over