rs1993477

chr8-102255838-A-C

Variant summary

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

The NM_015902.6(UBR5):c.8188-1324T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,014 control chromosomes in the GnomAD database, including 10,269 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 0.36 (10269 hom., cov: 31)
• Consequence: UBR5 NM_015902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR5	NM_015902.6	c.8188-1324T>G		intron_variant		ENST00000520539.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR5	ENST00000520539.6	c.8188-1324T>G		intron_variant		1	NM_015902.6	P5

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55023 AN: 151896 Hom.: 10252 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.362 AC: 55061 AN: 152014 Hom.: 10269 Cov.: 31 AF XY: 0.365 AC XY: 27112 AN XY: 74292

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.381

Alfa AF: 0.365 Hom.: 5600

Bravo AF: 0.361

Asia WGS AF: 0.310 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.66

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: rs1993477; hg19: chr8-103268066;