rs2293983

chr8-102293491-G-A

Variant summary

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

The NM_015902.6(UBR5):c.4589+114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,298,946 control chromosomes in the GnomAD database, including 3,866 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 0.051 (583 hom., cov: 32)
  • Exomes 𝑓: 0.036 (3283 hom.)
• Consequence: UBR5 NM_015902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779

Genes affected

UBR5 (HGNC:16806): (ubiquitin protein ligase E3 component n-recognin 5) This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation. [provided by RefSeq, Jul 2008]

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 = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR5	NM_015902.6	c.4589+114C>T		intron_variant		ENST00000520539.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR5	ENST00000520539.6	c.4589+114C>T		intron_variant		1	NM_015902.6	P5
UBR5	ENST00000220959.8	c.4589+114C>T		intron_variant		1		A1
UBR5	ENST00000521922.5	c.4571+114C>T		intron_variant		5		A1
UBR5	ENST00000519528.1	n.105+114C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7746 AN: 152130 Hom.: 578 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0556

GnomAD4 exome AF: 0.0356 AC: 40802 AN: 1146698 Hom.: 3283 AF XY: 0.0360 AC XY: 20415 AN XY: 567866

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0441

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.0644

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0488

GnomAD4 genome AF: 0.0511 AC: 7774 AN: 152248 Hom.: 583 Cov.: 32 AF XY: 0.0568 AC XY: 4225 AN XY: 74434

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.0922

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0278 Hom.: 155

Bravo AF: 0.0556

Asia WGS AF: 0.202 AC: 700 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	0.18
Dann	Benign	0.71

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: rs2293983; hg19: chr8-103305719; COSMIC: COSV55299841;