dbSNP rs1071745: UBC:p.Ile479Ile (chr12-124912335-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021009.7(UBC):c.1437T>C(p.Ile479Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0070 ( 71 hom. )

Failed GnomAD Quality Control

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.111

Publications

2 publications found

Variant links:

Genes affected

UBC (HGNC:12468): (ubiquitin C) This gene represents a ubiquitin gene, ubiquitin C. The encoded protein is a polyubiquitin precursor. Conjugation of ubiquitin monomers or polymers can lead to various effects within a cell, depending on the residues to which ubiquitin is conjugated. Ubiquitination has been associated with protein degradation, DNA repair, cell cycle regulation, kinase modification, endocytosis, and regulation of other cell signaling pathways. [provided by RefSeq, Aug 2010]

UBC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-124912335-A-G is Benign according to our data. Variant chr12-124912335-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 776775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021009.7. 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
	UBC	NM_021009.7	MANE Select	c.1437T>C	p.Ile479Ile	synonymous	Exon 2 of 2	NP_066289.3	P0CG48

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBC	ENST00000339647.6	TSL:1 MANE Select	c.1437T>C	p.Ile479Ile	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1	TSL:6	c.1437T>C	p.Ile479Ile	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
UBC	ENST00000874892.1		c.1437T>C	p.Ile479Ile	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

AN:

2730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0500

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.0556

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0357

GnomAD2 exomes

AF:

0.0346

AC:

1422

AN:

41076

AF XY:

0.0319

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0566

Gnomad EAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00769

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00700

AC:

1008

AN:

144004

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

480

AN XY:

80026

show subpopulations

African (AFR)

AF:

0.119

AC:

502

AN:

4204

American (AMR)

AF:

0.00781

AC:

149

AN:

19084

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

AN:

3814

East Asian (EAS)

AF:

0.00

AC:

AN:

5390

South Asian (SAS)

AF:

0.00147

AC:

AN:

19106

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

16134

Middle Eastern (MID)

AF:

0.00905

AC:

AN:

442

European-Non Finnish (NFE)

AF:

0.00270

AC:

190

AN:

70446

Other (OTH)

AF:

0.0121

AC:

AN:

5384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0323

AC:

AN:

2788

Hom.:

Cov.:

AF XY:

0.0339

AC XY:

AN XY:

1652

show subpopulations

African (AFR)

AF:

0.162

AC:

AN:

352

American (AMR)

AF:

0.0337

AC:

AN:

356

Ashkenazi Jewish (ASJ)

AF:

0.0500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00329

AC:

AN:

912

Middle Eastern (MID)

AF:

0.0455

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0140

AC:

AN:

926

Other (OTH)

AF:

0.0333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0593

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

3.4

(source)

DANN

Benign

0.41

PhyloP100

0.11

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