16-4874426-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001079514.3(UBN1):c.2016G>A(p.Ser672=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,104 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00065 (16 hom.)
• Consequence: UBN1 NM_001079514.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.14

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 16-4874426-G-A is Benign according to our data. Variant chr16-4874426-G-A is described in ClinVar as [Benign]. Clinvar id is 710341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.14 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0063 (960/152266) while in subpopulation AFR AF= 0.0219 (912/41558). AF 95% confidence interval is 0.0208. There are 8 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBN1	NM_001079514.3	c.2016G>A	p.Ser672=	synonymous_variant	15/18	ENST00000262376.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBN1	ENST00000262376.11	c.2016G>A	p.Ser672=	synonymous_variant	15/18	1	NM_001079514.3	P4
UBN1	ENST00000396658.8	c.2016G>A	p.Ser672=	synonymous_variant	14/17	1		P4
UBN1	ENST00000590769.5	c.2016G>A	p.Ser672=	synonymous_variant	15/17	2		A1
UBN1	ENST00000586716.1	c.396G>A	p.Ser132=	synonymous_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.00630 AC: 959 AN: 152148 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

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: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00163 AC: 409 AN: 251290 Hom.: 2 AF XY: 0.00119 AC XY: 162 AN XY: 135834

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000655 AC: 957 AN: 1461838 Hom.: 16 Cov.: 31 AF XY: 0.000578 AC XY: 420 AN XY: 727216

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00630 AC: 960 AN: 152266 Hom.: 8 Cov.: 33 AF XY: 0.00559 AC XY: 416 AN XY: 74454

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00282 Hom.: 0

Bravo AF: 0.00711

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.028
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs73517087; hg19: chr16-4924427;