Genetic Variant UBN1:p.Leu641Leu (chr16-4874333-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001079514.3(UBN1):c.1923C>T(p.Leu641Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,182 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 11 hom., cov: 33)

Exomes 𝑓: 0.010 ( 103 hom. )

Consequence

UBN1
NM_001079514.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.651

Variant links:

Genes affected

UBN1 (HGNC:12506): (ubinuclein 1) Cellular senescence is a hallmark of tumor suppression and tissue aging. Senescent cells contain domains of heterochromatin, called senescence-associated heterochromatin foci (SAHF), that repress proliferation-promoting genes. The protein encoded by this gene binds to proliferation-promoting genes and is required for SAHF formation, enhancing methylation of histone H3. [provided by RefSeq, Oct 2016]

UBN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 16-4874333-C-T is Benign according to our data. Variant chr16-4874333-C-T is described in ClinVar as [Benign]. Clinvar id is 781182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.651 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBN1	NM_001079514.3 link	c.1923C>T	p.Leu641Leu	synonymous_variant	Exon 15 of 18	ENST00000262376.11	NP_001072982.1	Q9NPG3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBN1	ENST00000262376.11 link	c.1923C>T	p.Leu641Leu	synonymous_variant	Exon 15 of 18	1	NM_001079514.3	ENSP00000262376.5	Q9NPG3-1
UBN1	ENST00000396658.8 link	c.1923C>T	p.Leu641Leu	synonymous_variant	Exon 14 of 17	1		ENSP00000379894.3	Q9NPG3-1
UBN1	ENST00000590769.5 link	c.1923C>T	p.Leu641Leu	synonymous_variant	Exon 15 of 17	2		ENSP00000468740.1	Q9NPG3-2
UBN1	ENST00000586716.1 link	c.300C>T	p.Leu100Leu	synonymous_variant	Exon 4 of 4	3		ENSP00000465309.1	K7EJT1

Frequencies

GnomAD3 genomes

AF:

0.00822

AC:

1251

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00840

AC:

2112

AN:

251416

Hom.:

AF XY:

0.00883

AC XY:

1200

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00438

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0103

AC:

15084

AN:

1461848

Hom.:

103

Cov.:

AF XY:

0.0102

AC XY:

7431

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00512

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00927

GnomAD4 genome

AF:

0.00823

AC:

1253

AN:

152334

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

631

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00847

Hom.:

Bravo

AF:

0.00669

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.00859

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 13, 2018

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

-0.70

CADD

Benign

4.3

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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