6-42564364-C-T

Variant names:

• chr6-42564364-C-T
• rs3749897
• NM_001363705.2:c.45C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.45C>T	p.Ser15Ser	synonymous_variant	Exon 1 of 47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.45C>T	p.Ser15Ser	synonymous_variant	Exon 1 of 47	5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.45C>T	p.Ser15Ser	synonymous_variant	Exon 1 of 47	1		ENSP00000361990.1
UBR2	ENST00000372903.6	c.45C>T	p.Ser15Ser	synonymous_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.426 AC: 103228 AN: 242226 AF XY: 0.425

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 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

African (AFR) AF: 0.506 AC: 16855 AN: 33294

American (AMR) AF: 0.408 AC: 17878 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 12225 AN: 25986

East Asian (EAS) AF: 0.462 AC: 18138 AN: 39250

South Asian (SAS) AF: 0.451 AC: 38506 AN: 85440

European-Finnish (FIN) AF: 0.448 AC: 23838 AN: 53228

Middle Eastern (MID) AF: 0.350 AC: 1986 AN: 5674

European-Non Finnish (NFE) AF: 0.410 AC: 455514 AN: 1109764

Other (OTH) AF: 0.422 AC: 25412 AN: 60164

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

African (AFR) AF: 0.507 AC: 20990 AN: 41434

American (AMR) AF: 0.424 AC: 6474 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2209 AN: 5122

South Asian (SAS) AF: 0.463 AC: 2223 AN: 4804

European-Finnish (FIN) AF: 0.451 AC: 4761 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28231 AN: 67914

Other (OTH) AF: 0.444 AC: 938 AN: 2114

Alfa AF: 0.430 Hom.: 9047

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
PhyloP100		2.2
PromoterAI		-0.053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3749897; hg19: chr6-42532102; COSMIC: COSV65769467;