rs6917033

Variant names:

• chr6-42659696-G-A
• rs6917033
• NM_001363705.2:c.3283G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-42659696-G-A
• chr6-42659696-G-C
• chr6-42659696-G-T

Variant summary

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

The NM_001363705.2(UBR2):​c.3283G>A​(p.Ala1095Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,610,270 control chromosomes in the GnomAD database, including 128,438 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (13722 hom., cov: 30)
  • Exomes 𝑓: 0.39 (114716 hom.)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 28 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7169118E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363705.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	NM_001363705.2	MANE Select	c.3283G>A	p.Ala1095Thr	missense	Exon 30 of 47	NP_001350634.1
	UBR2	NM_015255.3		c.3283G>A	p.Ala1095Thr	missense	Exon 30 of 47	NP_056070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.3283G>A	p.Ala1095Thr	missense	Exon 30 of 47	ENSP00000361992.1
	UBR2	ENST00000372899.6	TSL:1	c.3283G>A	p.Ala1095Thr	missense	Exon 30 of 47	ENSP00000361990.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64312 AN: 151512 Hom.: 13704 Cov.: 30

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.424

GnomAD2 exomes AF: 0.403 AC: 100849 AN: 250118 AF XY: 0.400

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.404

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.394 AC: 575271 AN: 1458640 Hom.: 114716 Cov.: 46 AF XY: 0.394 AC XY: 285818 AN XY: 725742

African (AFR) AF: 0.486 AC: 16267 AN: 33438

American (AMR) AF: 0.391 AC: 17477 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11560 AN: 26098

East Asian (EAS) AF: 0.450 AC: 17849 AN: 39648

South Asian (SAS) AF: 0.383 AC: 33014 AN: 86164

European-Finnish (FIN) AF: 0.431 AC: 23007 AN: 53354

Middle Eastern (MID) AF: 0.328 AC: 1892 AN: 5768

European-Non Finnish (NFE) AF: 0.388 AC: 430310 AN: 1109268

Other (OTH) AF: 0.397 AC: 23895 AN: 60260

GnomAD4 genome AF: 0.424 AC: 64359 AN: 151630 Hom.: 13722 Cov.: 30 AF XY: 0.424 AC XY: 31423 AN XY: 74044

African (AFR) AF: 0.485 AC: 20055 AN: 41318

American (AMR) AF: 0.405 AC: 6168 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1521 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2186 AN: 5166

South Asian (SAS) AF: 0.394 AC: 1892 AN: 4808

European-Finnish (FIN) AF: 0.435 AC: 4548 AN: 10450

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26730 AN: 67878

Other (OTH) AF: 0.420 AC: 882 AN: 2098

Alfa AF: 0.400 Hom.: 43184

Bravo AF: 0.425

TwinsUK AF: 0.407 AC: 1509

ALSPAC AF: 0.387 AC: 1490

ESP6500AA AF: 0.482 AC: 2124

ESP6500EA AF: 0.392 AC: 3370

ExAC AF: 0.404 AC: 49037

Asia WGS AF: 0.414 AC: 1436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.89
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.00017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.054
Sift	Benign	0.40	T
Sift4G	Benign	0.44	T
Polyphen		0.091	B
Vest4		0.016
MPC		0.39
ClinPred		0.0019	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.012
gMVP		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6917033; hg19: chr6-42627434; COSMIC: COSV65750383; COSMIC: COSV65750383;