rs1045643

Positions:

• chr16-4881512-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079514.3(UBN1):​c.*1380C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,098 control chromosomes in the GnomAD database, including 1,603 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1603 hom., cov: 31)
  • Exomes 𝑓: 0.094 (0 hom.)
• Consequence: UBN1 NM_001079514.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBN1	NM_001079514.3	c.*1380C>T		3_prime_UTR_variant	18/18	ENST00000262376.11	NP_001072982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBN1	ENST00000262376.11	c.*1380C>T		3_prime_UTR_variant	18/18	1	NM_001079514.3	ENSP00000262376	P4
UBN1	ENST00000396658.8	c.*1380C>T		3_prime_UTR_variant	17/17	1		ENSP00000379894	P4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20765 AN: 151948 Hom.: 1589 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0938 AC: 3 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.150 AC XY: 3 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.137 AC: 20815 AN: 152066 Hom.: 1603 Cov.: 31 AF XY: 0.138 AC XY: 10222 AN XY: 74328

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0879

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.148

Alfa AF: 0.139 Hom.: 1664

Bravo AF: 0.146

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.57
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: rs1045643; hg19: chr16-4931513;