dbSNP rs7969431: UBE2N:c.418+17C>T (chr12-93410717-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003348.4(UBE2N):c.418+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,613,750 control chromosomes in the GnomAD database, including 311 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 0.014 ( 24 hom., cov: 33)

Exomes 𝑓: 0.017 ( 287 hom. )

Consequence

UBE2N
NM_003348.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.121

Publications

6 publications found

Variant links:

Genes affected

UBE2N (HGNC:12492): (ubiquitin conjugating enzyme E2 N) 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. Studies in mouse suggest that this protein plays a role in DNA postreplication repair. [provided by RefSeq, Jul 2008]

UBE2N 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=-0.77).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2194/152334) while in subpopulation NFE AF = 0.0187 (1269/68040). AF 95% confidence interval is 0.0178. There are 24 homozygotes in GnomAd4. There are 1089 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2194 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2N	NM_003348.4	MANE Select	c.418+17C>T		intron	N/A	NP_003339.1	P61088

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE2N	ENST00000318066.7	TSL:1 MANE Select	c.418+17C>T	intron	N/A	ENSP00000316176.2	P61088
UBE2N	ENST00000550657.1	TSL:2	c.*154C>T	3_prime_UTR	Exon 2 of 2	ENSP00000449352.1	F8VV71
UBE2N	ENST00000934316.1		c.418+17C>T	intron	N/A	ENSP00000604375.1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2195

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00376

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0150

AC:

3756

AN:

250860

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0255

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0224

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0169

AC:

24771

AN:

1461416

Hom.:

287

Cov.:

AF XY:

0.0169

AC XY:

12302

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.00332

AC:

111

AN:

33468

American (AMR)

AF:

0.0126

AC:

562

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0272

AC:

709

AN:

26114

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.00717

AC:

618

AN:

86242

European-Finnish (FIN)

AF:

0.0219

AC:

1170

AN:

53404

Middle Eastern (MID)

AF:

0.0340

AC:

196

AN:

5764

European-Non Finnish (NFE)

AF:

0.0183

AC:

20356

AN:

1111654

Other (OTH)

AF:

0.0173

AC:

1047

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1319

2637

3956

5274

6593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.0144

AC:

2194

AN:

152334

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1089

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00375

AC:

156

AN:

41570

American (AMR)

AF:

0.0164

AC:

251

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00497

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0225

AC:

239

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1269

AN:

68040

Other (OTH)

AF:

0.0199

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

224

335

447

559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0170

Hom.:

Bravo

AF:

0.0136

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.12

Mutation Taster

=99/1

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