rs10505029

chr8-102394898-T-C

Variant summary

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

The NM_015902.6(UBR5):c.62+17275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,310 control chromosomes in the GnomAD database, including 984 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 0.097 (984 hom., cov: 33)
• Consequence: UBR5 NM_015902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR5	NM_015902.6	c.62+17275A>G		intron_variant		ENST00000520539.6
UBR5	NM_001282873.2	c.62+17275A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR5	ENST00000520539.6	c.62+17275A>G		intron_variant		1	NM_015902.6	P5
UBR5	ENST00000220959.8	c.62+17275A>G		intron_variant		1		A1
UBR5	ENST00000521922.5	c.62+17275A>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0970 AC: 14768 AN: 152192 Hom.: 979 Cov.: 33

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0334

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0970 AC: 14775 AN: 152310 Hom.: 984 Cov.: 33 AF XY: 0.0997 AC XY: 7422 AN XY: 74476

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.0843

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.110

Alfa AF: 0.114 Hom.: 1542

Bravo AF: 0.101

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.19
Dann	Benign	0.81

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: rs10505029; hg19: chr8-103407126;