rs1545725

Variant names:

• chr2-170061807-C-G
• rs1545725
• NM_172070.4:c.5019+364C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172070.4(UBR3):​c.5019+364C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,170 control chromosomes in the GnomAD database, including 385 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 0.051 (385 hom., cov: 32)
• Consequence: UBR3 NM_172070.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 0 publications found

Genes affected

UBR3 (HGNC:30467): (ubiquitin protein ligase E3 component n-recognin 3) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; sensory perception of smell; and suckling behavior. Predicted to act upstream of or within in utero embryonic development and olfactory behavior. Predicted to be integral component of membrane. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR3	NM_172070.4	c.5019+364C>G		intron_variant	Intron 35 of 38	ENST00000272793.11	NP_742067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR3	ENST00000272793.11	c.5019+364C>G		intron_variant	Intron 35 of 38	5	NM_172070.4	ENSP00000272793.5

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7749 AN: 152052 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0510 AC: 7755 AN: 152170 Hom.: 385 Cov.: 32 AF XY: 0.0493 AC XY: 3665 AN XY: 74400

African (AFR) AF: 0.132 AC: 5484 AN: 41488

American (AMR) AF: 0.0358 AC: 547 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5188

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4828

European-Finnish (FIN) AF: 0.0199 AC: 210 AN: 10578

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0185 AC: 1255 AN: 68010

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

Alfa AF: 0.0375 Hom.: 25

Bravo AF: 0.0572

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.37
PhyloP100		-1.1
Mutation Taster		=99/1	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: rs1545725; hg19: chr2-170918317;