rs6714222

Positions:

• chr2-169953849-G-A
• chr2-169953849-G-C
• chr2-169953849-G-T

Variant summary

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

The NM_172070.4(UBR3):​c.3545+3784G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,194 control chromosomes in the GnomAD database, including 401 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 0.054 (401 hom., cov: 32)
• Consequence: UBR3 NM_172070.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR3	NM_172070.4	c.3545+3784G>A		intron_variant		ENST00000272793.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR3	ENST00000272793.11	c.3545+3784G>A		intron_variant		5	NM_172070.4	P1
UBR3	ENST00000392632.6	c.718+3784G>A		intron_variant		5
UBR3	ENST00000430321.5	c.987+3784G>A		intron_variant, NMD_transcript_variant		5
UBR3	ENST00000487689.1	n.584+3784G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8215 AN: 152076 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0470

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

GnomAD4 genome AF: 0.0540 AC: 8220 AN: 152194 Hom.: 401 Cov.: 32 AF XY: 0.0524 AC XY: 3899 AN XY: 74418

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.00998 Hom.: 3

Bravo AF: 0.0604

Asia WGS AF: 0.0330 AC: 114 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.61

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: rs6714222; hg19: chr2-170810359;