6-42564364-C-T

Position:

• chr6-42564364-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001363705.2(UBR2):​c.45C>T​(p.Ser15Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,608,534 control chromosomes in the GnomAD database, including 144,425 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 0.45 (15220 hom., cov: 32)
  • Exomes 𝑓: 0.42 (129205 hom.)
• Consequence: UBR2 NM_001363705.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

Genes affected

UBR2 (HGNC:21289): (ubiquitin protein ligase E3 component n-recognin 2) Enables leucine binding activity. Involved in cellular response to leucine and negative regulation of TOR signaling. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. Predicted to colocalize with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=2.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.45C>T	p.Ser15Ser	synonymous_variant	1/47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.45C>T	p.Ser15Ser	synonymous_variant	1/47	5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.45C>T	p.Ser15Ser	synonymous_variant	1/47	1		ENSP00000361990.1
UBR2	ENST00000372903.6	c.45C>T	p.Ser15Ser	synonymous_variant	1/12	1		ENSP00000361994.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67772 AN: 151782 Hom.: 15203 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.447

GnomAD3 exomes AF: 0.426 AC: 103228 AN: 242226 Hom.: 22161 AF XY: 0.425 AC XY: 55864 AN XY: 131388

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.404

Gnomad SAS exome AF: 0.455

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.419 AC: 610352 AN: 1456634 Hom.: 129205 Cov.: 55 AF XY: 0.420 AC XY: 304171 AN XY: 724452

Gnomad4 AFR exome AF: 0.506

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.447 AC: 67827 AN: 151900 Hom.: 15220 Cov.: 32 AF XY: 0.446 AC XY: 33119 AN XY: 74252

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.444

Alfa AF: 0.430 Hom.: 6704

Bravo AF: 0.445

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3749897; hg19: chr6-42532102; COSMIC: COSV65769467;