Genetic Variant NM_003344.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UBE2H	NM_003344.4 link	c.246-95G>A	intron_variant	Intron 4 of 6	ENST00000355621.8	NP_003335.1	P62256-1A4D1L5
UBE2H	NM_182697.3 link	c.206-18323G>A	intron_variant	Intron 3 of 4		NP_874356.1	P62256-2
UBE2H	NM_001202498.2 link	c.36-95G>A	intron_variant	Intron 4 of 6		NP_001189427.1	P62256A0A3B3IU20
UBE2H	XM_047420796.1 link	c.36-95G>A	intron_variant	Intron 5 of 7		XP_047276752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2H	ENST00000355621.8 link	c.246-95G>A		intron_variant	Intron 4 of 6	1	NM_003344.4	ENSP00000347836.3		P62256-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over