2-170076012-T-G

Position:

• chr2-170076012-T-G

Variant summary

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

The NM_172070.4(UBR3):​c.5199+2405T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 151,904 control chromosomes in the GnomAD database, including 47,815 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 0.79 (47815 hom., cov: 30)
• Consequence: UBR3 NM_172070.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR3	NM_172070.4	c.5199+2405T>G		intron_variant		ENST00000272793.11	NP_742067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR3	ENST00000272793.11	c.5199+2405T>G		intron_variant		5	NM_172070.4	ENSP00000272793	P1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119720 AN: 151786 Hom.: 47795 Cov.: 30

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.789 AC: 119786 AN: 151904 Hom.: 47815 Cov.: 30 AF XY: 0.787 AC XY: 58371 AN XY: 74216

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.813

Alfa AF: 0.847 Hom.: 72064

Bravo AF: 0.778

Asia WGS AF: 0.843 AC: 2930 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	9.3
DANN	Benign	0.80

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: rs10204475; hg19: chr2-170932522;