6-42675330-A-G

Variant names:

• chr6-42675330-A-G
• rs11751656
• NM_001363705.2:c.4252-726A>G

Variant summary

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

The NM_001363705.2(UBR2):​c.4252-726A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,258 control chromosomes in the GnomAD database, including 378 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 0.062 (378 hom., cov: 32)
• Consequence: UBR2 NM_001363705.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 5 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 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.4252-726A>G		intron	N/A	NP_001350634.1
	UBR2	NM_015255.3		c.4252-726A>G		intron	N/A	NP_056070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.4252-726A>G		intron	N/A	ENSP00000361992.1
	UBR2	ENST00000372899.6	TSL:1	c.4252-726A>G		intron	N/A	ENSP00000361990.1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9424 AN: 152140 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0619 AC: 9421 AN: 152258 Hom.: 378 Cov.: 32 AF XY: 0.0603 AC XY: 4490 AN XY: 74438

African (AFR) AF: 0.0169 AC: 701 AN: 41564

American (AMR) AF: 0.0599 AC: 916 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0871 AC: 302 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4824

European-Finnish (FIN) AF: 0.0963 AC: 1021 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6155 AN: 68012

Other (OTH) AF: 0.0682 AC: 144 AN: 2110

Alfa AF: 0.0707 Hom.: 51

Bravo AF: 0.0591

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.014
DANN	Benign	0.61
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11751656; hg19: chr6-42643068;