rs2905

Variant names:

• chr14-93227076-C-T
• rs2905
• NM_175748.4:c.*41C>T

Variant summary

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

The NM_175748.4(UBR7):​c.*41C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,459,678 control chromosomes in the GnomAD database, including 71,536 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 0.24 (5667 hom., cov: 32)
  • Exomes 𝑓: 0.31 (65869 hom.)
• Consequence: UBR7 NM_175748.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671
• Publications: 40 publications found

Genes affected

UBR7 (HGNC:20344): (ubiquitin protein ligase E3 component n-recognin 7) This gene encodes a UBR box-containing protein that belongs to the E3 ubiquitin ligase family. The protein also contains a plant homeodomain (PHD) in the C-terminus. In mammals, the encoded protein recognizes N-degrons, the destabilizing N-terminal residues of short-lived proteins, which results in ubiquitinylation, and proteolysis via the proteasome. [provided by RefSeq, Jul 2016]

UBR7 Gene-Disease associations (from GenCC):

• Li-Campeau syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175748.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	NM_175748.4	MANE Select	c.*41C>T		3_prime_UTR	Exon 11 of 11	NP_786924.2	Q8N806
	UBR7	NR_038150.2		n.1221C>T		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	ENST00000013070.11	TSL:1 MANE Select	c.*41C>T		3_prime_UTR	Exon 11 of 11	ENSP00000013070.6	Q8N806
	UBR7	ENST00000966805.1		c.*41C>T		3_prime_UTR	Exon 11 of 11	ENSP00000636864.1
	UBR7	ENST00000940497.1		c.*41C>T		3_prime_UTR	Exon 11 of 11	ENSP00000610556.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37148 AN: 151916 Hom.: 5670 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.279 AC: 68487 AN: 245880 AF XY: 0.279

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.310 AC: 405656 AN: 1307644 Hom.: 65869 Cov.: 17 AF XY: 0.307 AC XY: 202225 AN XY: 658334

African (AFR) AF: 0.0544 AC: 1634 AN: 30056

American (AMR) AF: 0.257 AC: 11289 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 8387 AN: 24864

East Asian (EAS) AF: 0.246 AC: 9390 AN: 38130

South Asian (SAS) AF: 0.179 AC: 14785 AN: 82486

European-Finnish (FIN) AF: 0.321 AC: 16359 AN: 50998

Middle Eastern (MID) AF: 0.258 AC: 1406 AN: 5452

European-Non Finnish (NFE) AF: 0.334 AC: 326116 AN: 976928

Other (OTH) AF: 0.298 AC: 16290 AN: 54756

GnomAD4 genome AF: 0.244 AC: 37140 AN: 152034 Hom.: 5667 Cov.: 32 AF XY: 0.246 AC XY: 18269 AN XY: 74332

African (AFR) AF: 0.0658 AC: 2731 AN: 41496

American (AMR) AF: 0.292 AC: 4459 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1291 AN: 5160

South Asian (SAS) AF: 0.173 AC: 833 AN: 4812

European-Finnish (FIN) AF: 0.319 AC: 3368 AN: 10554

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22514 AN: 67952

Other (OTH) AF: 0.247 AC: 520 AN: 2108

Alfa AF: 0.307 Hom.: 16590

Bravo AF: 0.233

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.67
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: rs2905; hg19: chr14-93693422; COSMIC: COSV50152162; COSMIC: COSV50152162;