Variant 16-4874279-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001079514.3(UBN1):c.1869G>C(p.Leu623Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000361 in 1,613,490 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

UBN1
NM_001079514.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066578686).

BP6

Variant 16-4874279-G-C is Benign according to our data. Variant chr16-4874279-G-C is described in ClinVar as [Benign]. Clinvar id is 727127.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBN1	NM_001079514.3 linkuse as main transcript	c.1869G>C	p.Leu623Phe	missense_variant	15/18	ENST00000262376.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBN1	ENST00000262376.11 linkuse as main transcript	c.1869G>C	p.Leu623Phe	missense_variant	15/18	1	NM_001079514.3	P4	Q9NPG3-1
UBN1	ENST00000396658.8 linkuse as main transcript	c.1869G>C	p.Leu623Phe	missense_variant	14/17	1		P4	Q9NPG3-1
UBN1	ENST00000590769.5 linkuse as main transcript	c.1869G>C	p.Leu623Phe	missense_variant	15/17	2		A1	Q9NPG3-2
UBN1	ENST00000586716.1 linkuse as main transcript	c.249G>C	p.Leu83Phe	missense_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

278

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000538

AC:

135

AN:

250708

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000208

AC:

304

AN:

1461164

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.00825

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.00183

AC:

278

AN:

152326

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.00209

ESP6500AA

AF:

0.00683

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000601

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.024

MetaRNN

Benign

0.0067

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.7

N;.;N

REVEL

Benign

0.15

Sift

Benign

0.049

D;.;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.40

MutPred

0.15

Loss of stability (P = 0.1827);Loss of stability (P = 0.1827);Loss of stability (P = 0.1827);

MVP

0.16

MPC

0.37

ClinPred

0.033

GERP RS

4.6

Varity_R

0.082

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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