rs1993477

Variant names:

• chr8-102255838-A-C
• rs1993477
• NM_015902.6:c.8188-1324T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

UBR5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015902.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR5	NM_015902.6	MANE Select	c.8188-1324T>G		intron	N/A	NP_056986.2
	UBR5	NM_001282873.2		c.8185-1324T>G		intron	N/A	NP_001269802.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR5	ENST00000520539.6	TSL:1 MANE Select	c.8188-1324T>G		intron	N/A	ENSP00000429084.1
	UBR5	ENST00000220959.8	TSL:1	c.8185-1324T>G		intron	N/A	ENSP00000220959.4
	UBR5	ENST00000521922.5	TSL:5	c.8167-1324T>G		intron	N/A	ENSP00000427819.1

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

African (AFR) AF: 0.343 AC: 14223 AN: 41472

American (AMR) AF: 0.412 AC: 6292 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3468

East Asian (EAS) AF: 0.128 AC: 662 AN: 5180

South Asian (SAS) AF: 0.391 AC: 1884 AN: 4818

European-Finnish (FIN) AF: 0.429 AC: 4524 AN: 10536

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24751 AN: 67960

Other (OTH) AF: 0.381 AC: 805 AN: 2112

Alfa AF: 0.362 Hom.: 20747

Bravo AF: 0.361

Asia WGS AF: 0.310 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs1993477; hg19: chr8-103268066;