rs2905

Positions:

• chr14-93227076-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-93227076-C-T is Benign according to our data. Variant chr14-93227076-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR7	NM_175748.4	c.*41C>T		3_prime_UTR_variant	11/11	ENST00000013070.11	NP_786924.2
UBR7	NR_038150.2	n.1221C>T		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR7	ENST00000013070.11	c.*41C>T		3_prime_UTR_variant	11/11	1	NM_175748.4	ENSP00000013070.6
UBR7	ENST00000555329.1	c.*41C>T		3_prime_UTR_variant	4/4	4		ENSP00000452488.1
UBR7	ENST00000553674.1	n.*1020C>T		non_coding_transcript_exon_variant	10/10	2		ENSP00000450470.1
UBR7	ENST00000553674.1	n.*1020C>T		3_prime_UTR_variant	10/10	2		ENSP00000450470.1

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

GnomAD3 exomes AF: 0.279 AC: 68487 AN: 245880 Hom.: 10179 AF XY: 0.279 AC XY: 37109 AN XY: 133162

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 SAS exome AF: 0.177

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

Gnomad4 AFR exome AF: 0.0544

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.298

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

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.247

Alfa AF: 0.316 Hom.: 12045

Bravo AF: 0.233

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.64

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: rs2905; hg19: chr14-93693422; COSMIC: COSV50152162; COSMIC: COSV50152162;