16-4855123-A-G

Position:

• chr16-4855123-A-G

Variant summary

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

The NM_001079514.3(UBN1):​c.249+1957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,416 control chromosomes in the GnomAD database, including 25,585 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 0.56 (25585 hom., cov: 30)
• Consequence: UBN1 NM_001079514.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBN1	NM_001079514.3	c.249+1957A>G		intron_variant		ENST00000262376.11	NP_001072982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBN1	ENST00000262376.11	c.249+1957A>G		intron_variant		1	NM_001079514.3	ENSP00000262376.5
UBN1	ENST00000396658.8	c.249+1957A>G		intron_variant		1		ENSP00000379894.3
UBN1	ENST00000590769.5	c.249+1957A>G		intron_variant		2		ENSP00000468740.1
UBN1	ENST00000592120.5	c.249+1957A>G		intron_variant		2		ENSP00000467942.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85271 AN: 151298 Hom.: 25531 Cov.: 30

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85382 AN: 151416 Hom.: 25585 Cov.: 30 AF XY: 0.562 AC XY: 41570 AN XY: 73944

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.557

Alfa AF: 0.525 Hom.: 3837

Bravo AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.2
DANN	Benign	0.67

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: rs9923349; hg19: chr16-4905124;