6-42691014-T-C

Position:

• chr6-42691014-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.5127-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,612,290 control chromosomes in the GnomAD database, including 209,968 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 0.50 (19330 hom., cov: 32)
  • Exomes 𝑓: 0.51 (190638 hom.)
• Consequence: UBR2 NM_001363705.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.5127-18T>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.5127-18T>C		intron_variant		5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.5127-18T>C		intron_variant		1		ENSP00000361990.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76198 AN: 151928 Hom.: 19320 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.494

GnomAD3 exomes AF: 0.489 AC: 122312 AN: 250142 Hom.: 30728 AF XY: 0.496 AC XY: 67073 AN XY: 135328

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.392

Gnomad SAS exome AF: 0.525

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.509 AC: 742951 AN: 1460244 Hom.: 190638 Cov.: 39 AF XY: 0.510 AC XY: 370420 AN XY: 726534

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.501 AC: 76233 AN: 152046 Hom.: 19330 Cov.: 32 AF XY: 0.499 AC XY: 37068 AN XY: 74318

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.500

Alfa AF: 0.508 Hom.: 23953

Bravo AF: 0.484

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.77

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: rs373341; hg19: chr6-42658752; COSMIC: COSV65750044;