chr16-4874426-G-A

Variant names:

• chr16-4874426-G-A
• rs73517087
• NM_001079514.3:c.2016G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001079514.3(UBN1):​c.2016G>A​(p.Ser672Ser) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.14
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -21 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 VariationId is 710341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 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.2016G>A	p.Ser672Ser	synonymous	Exon 15 of 18	NP_001072982.1	Q9NPG3-1
	UBN1	NM_001288656.1		c.2016G>A	p.Ser672Ser	synonymous	Exon 15 of 17	NP_001275585.1	Q9NPG3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBN1	ENST00000262376.11	TSL:1 MANE Select	c.2016G>A	p.Ser672Ser	synonymous	Exon 15 of 18	ENSP00000262376.5	Q9NPG3-1
	UBN1	ENST00000396658.8	TSL:1	c.2016G>A	p.Ser672Ser	synonymous	Exon 14 of 17	ENSP00000379894.3	Q9NPG3-1
	UBN1	ENST00000931634.1		c.1989G>A	p.Ser663Ser	synonymous	Exon 15 of 18	ENSP00000601693.1

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

GnomAD2 exomes AF: 0.00163 AC: 409 AN: 251290 AF XY: 0.00119

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 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

African (AFR) AF: 0.0231 AC: 775 AN: 33480

American (AMR) AF: 0.00116 AC: 52 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111986

Other (OTH) AF: 0.00131 AC: 79 AN: 60396

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

African (AFR) AF: 0.0219 AC: 912 AN: 41558

American (AMR) AF: 0.00248 AC: 38 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00281 Hom.: 2

Bravo AF: 0.00711

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.028
DANN	Benign	0.62
PhyloP100		-5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs73517087; hg19: chr16-4924427;