Genetic Variant NM_001079514.3:c.1923C>T (chr16-4874333-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079514.3. 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
	UBN1	NM_001079514.3	MANE Select	c.1923C>T	p.Leu641Leu	synonymous	Exon 15 of 18	NP_001072982.1	Q9NPG3-1
	UBN1	NM_001288656.1		c.1923C>T	p.Leu641Leu	synonymous	Exon 15 of 17	NP_001275585.1	Q9NPG3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBN1	ENST00000262376.11	TSL:1 MANE Select	c.1923C>T	p.Leu641Leu	synonymous	Exon 15 of 18	ENSP00000262376.5	Q9NPG3-1
UBN1	ENST00000396658.8	TSL:1	c.1923C>T	p.Leu641Leu	synonymous	Exon 14 of 17	ENSP00000379894.3	Q9NPG3-1
UBN1	ENST00000931634.1		c.1896C>T	p.Leu632Leu	synonymous	Exon 15 of 18	ENSP00000601693.1

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

GnomAD2 exomes

AF:

0.00840

AC:

2112

AN:

251416

AF XY:

0.00883

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 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

African (AFR)

AF:

0.00146

AC:

AN:

33480

American (AMR)

AF:

0.00369

AC:

165

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00486

AC:

127

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00512

AC:

442

AN:

86258

European-Finnish (FIN)

AF:

0.0219

AC:

1169

AN:

53376

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0113

AC:

12562

AN:

1112012

Other (OTH)

AF:

0.00927

AC:

560

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

995

1990

2985

3980

4975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.00823

AC:

1253

AN:

152334

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

631

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41574

American (AMR)

AF:

0.00503

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00394

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0250

AC:

265

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

779

AN:

68038

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

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

ClinVar submissions

Significance: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

-0.70

CADD

Benign

4.3

(source)

DANN

Benign

0.68

PhyloP100

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(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