chr6-42600510-T-C

Position:

• chr6-42600510-T-C

Variant summary

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

The NM_001363705.2(UBR2):​c.532-3078T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 151,754 control chromosomes in the GnomAD database, including 43,433 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 0.75 (43433 hom., cov: 29)
• Consequence: UBR2 NM_001363705.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.532-3078T>C		intron_variant		ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.532-3078T>C		intron_variant		5	NM_001363705.2	ENSP00000361992	P3
UBR2	ENST00000372899.6	c.532-3078T>C		intron_variant		1		ENSP00000361990	A1
UBR2	ENST00000372903.6	c.532-3078T>C		intron_variant		1		ENSP00000361994

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114170 AN: 151638 Hom.: 43384 Cov.: 29

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.753 AC: 114279 AN: 151754 Hom.: 43433 Cov.: 29 AF XY: 0.752 AC XY: 55760 AN XY: 74134

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.755

Alfa AF: 0.740 Hom.: 7077

Bravo AF: 0.746

Asia WGS AF: 0.698 AC: 2425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.59

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: rs2025249; hg19: chr6-42568248; COSMIC: COSV65767649;