rs7840202

Variant names:

• chr8-102296172-A-C
• rs7840202
• NM_015902.6:c.3666-390T>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.3666-390T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,128 control chromosomes in the GnomAD database, including 4,028 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 0.21 (4028 hom., cov: 32)
• Consequence: UBR5 NM_015902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.288 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR5	NM_015902.6	MANE Select	c.3666-390T>G		intron	N/A	NP_056986.2
	UBR5	NM_001282873.2		c.3666-390T>G		intron	N/A	NP_001269802.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR5	ENST00000520539.6	TSL:1 MANE Select	c.3666-390T>G		intron	N/A	ENSP00000429084.1
	UBR5	ENST00000220959.8	TSL:1	c.3666-390T>G		intron	N/A	ENSP00000220959.4
	UBR5	ENST00000926954.1		c.3666-390T>G		intron	N/A	ENSP00000597013.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32292 AN: 152010 Hom.: 4029 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0465

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.212 AC: 32280 AN: 152128 Hom.: 4028 Cov.: 32 AF XY: 0.207 AC XY: 15389 AN XY: 74346

African (AFR) AF: 0.105 AC: 4376 AN: 41538

American (AMR) AF: 0.231 AC: 3518 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3468

East Asian (EAS) AF: 0.0464 AC: 240 AN: 5176

South Asian (SAS) AF: 0.0903 AC: 436 AN: 4828

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10584

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19797 AN: 67958

Other (OTH) AF: 0.196 AC: 415 AN: 2114

Alfa AF: 0.263 Hom.: 3374

Bravo AF: 0.210

Asia WGS AF: 0.0840 AC: 290 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	0.39
DANN	Benign	0.38
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7840202; hg19: chr8-103308400;