chr8-102394898-T-C

Variant names:

• chr8-102394898-T-C
• rs10505029
• NM_015902.6:c.62+17275A>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.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
• Publications: 1 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=-0.92).
• 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 rank	MANE	Protein	UniProt
UBR5	NM_015902.6	c.62+17275A>G		intron_variant	Intron 1 of 58	ENST00000520539.6	NP_056986.2
UBR5	NM_001282873.2	c.62+17275A>G		intron_variant	Intron 1 of 58		NP_001269802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR5	ENST00000520539.6	c.62+17275A>G		intron_variant	Intron 1 of 58	1	NM_015902.6	ENSP00000429084.1
UBR5	ENST00000220959.8	c.62+17275A>G		intron_variant	Intron 1 of 58	1		ENSP00000220959.4
UBR5	ENST00000521922.5	c.62+17275A>G		intron_variant	Intron 1 of 58	5		ENSP00000427819.1

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

African (AFR) AF: 0.0435 AC: 1809 AN: 41580

American (AMR) AF: 0.207 AC: 3161 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.0333 AC: 173 AN: 5190

South Asian (SAS) AF: 0.176 AC: 847 AN: 4818

European-Finnish (FIN) AF: 0.0843 AC: 894 AN: 10610

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7134 AN: 68028

Other (OTH) AF: 0.110 AC: 233 AN: 2116

Alfa AF: 0.109 Hom.: 3316

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
PhyloP100		-0.72
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: rs10505029; hg19: chr8-103407126;