6-42691014-T-C

Variant names:

• chr6-42691014-T-C
• rs373341
• NM_001363705.2:c.5127-18T>C

Variant summary

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

The NM_015255.3(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_015255.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 10 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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015255.3. 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.5127-18T>C		intron	N/A	NP_001350634.1
	UBR2	NM_015255.3		c.5127-18T>C		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.5127-18T>C		intron	N/A	ENSP00000361992.1
	UBR2	ENST00000372899.6	TSL:1	c.5127-18T>C		intron	N/A	ENSP00000361990.1
	UBR2	ENST00000910623.1		c.5124-18T>C		intron	N/A	ENSP00000580682.1

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

GnomAD2 exomes AF: 0.489 AC: 122312 AN: 250142 AF XY: 0.496

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 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

African (AFR) AF: 0.481 AC: 16068 AN: 33378

American (AMR) AF: 0.350 AC: 15482 AN: 44220

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 13076 AN: 26092

East Asian (EAS) AF: 0.418 AC: 16581 AN: 39688

South Asian (SAS) AF: 0.519 AC: 44701 AN: 86138

European-Finnish (FIN) AF: 0.569 AC: 30403 AN: 53396

Middle Eastern (MID) AF: 0.503 AC: 2897 AN: 5762

European-Non Finnish (NFE) AF: 0.516 AC: 572928 AN: 1111254

Other (OTH) AF: 0.511 AC: 30815 AN: 60316

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

African (AFR) AF: 0.484 AC: 20044 AN: 41442

American (AMR) AF: 0.423 AC: 6459 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3472

East Asian (EAS) AF: 0.406 AC: 2102 AN: 5178

South Asian (SAS) AF: 0.520 AC: 2503 AN: 4816

European-Finnish (FIN) AF: 0.568 AC: 6004 AN: 10570

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35796 AN: 67982

Other (OTH) AF: 0.500 AC: 1054 AN: 2108

Alfa AF: 0.507 Hom.: 31902

Bravo AF: 0.484

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.23
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: rs373341; hg19: chr6-42658752; COSMIC: COSV65750044;