17-16381964-C-T

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

2

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]

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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
UBBNM_018955.4 linkc.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
UBBENST00000302182.8 linkc.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.:
26
Cov.:
32
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.:
8
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.:
16
Cov.:
30
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.:
26
Cov.:
32
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.:
2
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

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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.

Other links and lift over

dbSNP: rs151174232; hg19: chr17-16285278; API