Genetic Variant UBB:p.Pro19Pro (chr17-16381964-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_018955.4(UBB):c.57C>T(p.Pro19Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,614,126 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0097 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 16 hom. )

Consequence

UBB
NM_018955.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.680

Variant links:

Genes affected

UBB (HGNC:12463): (ubiquitin B) This gene encodes ubiquitin, one of the most conserved proteins known. Ubiquitin has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene consists of three direct repeats of the ubiquitin coding sequence with no spacer sequence. Consequently, the protein is expressed as a polyubiquitin precursor with a final amino acid after the last repeat. An aberrant form of this protein has been detected in patients with Alzheimer's disease and Down syndrome. Pseudogenes of this gene are located on chromosomes 1, 2, 13, and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

UBB links:

ENSG00000265401 (HGNC:):

ENSG00000265401 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 17-16381964-C-T is Benign according to our data. Variant chr17-16381964-C-T is described in ClinVar as [Benign]. Clinvar id is 716463.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00968 (1474/152272) while in subpopulation AFR AF= 0.0338 (1406/41538). AF 95% confidence interval is 0.0324. There are 26 homozygotes in gnomad4. There are 680 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1474 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBB	NM_018955.4 link	c.57C>T	p.Pro19Pro	synonymous_variant	Exon 2 of 2	ENST00000302182.8	NP_061828.1	P0CG47Q5U5U6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBB	ENST00000302182.8 link	c.57C>T	p.Pro19Pro	synonymous_variant	Exon 2 of 2	1	NM_018955.4	ENSP00000304697.3		P0CG47

Frequencies

GnomAD3 genomes

AF:

0.00967

AC:

1472

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00283

AC:

711

AN:

251482

Hom.:

AF XY:

0.00204

AC XY:

277

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0364

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00107

AC:

1559

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000925

AC XY:

673

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.00296

GnomAD4 genome

AF:

0.00968

AC:

1474

AN:

152272

Hom.:

Cov.:

AF XY:

0.00913

AC XY:

680

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00577

Hom.:

Bravo

AF:

0.0110

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.7

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over