rs17128941

Positions:

• chr14-93218751-C-T

Variant summary

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

The NM_175748.4(UBR7):​c.810+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,608,994 control chromosomes in the GnomAD database, including 7,927 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 0.11 (953 hom., cov: 32)
  • Exomes 𝑓: 0.095 (6974 hom.)
• Consequence: UBR7 NM_175748.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR7	NM_175748.4	c.810+16C>T		intron_variant		ENST00000013070.11	NP_786924.2
UBR7	NR_038150.2	n.712+16C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR7	ENST00000013070.11	c.810+16C>T		intron_variant		1	NM_175748.4	ENSP00000013070.6
UBR7	ENST00000553857.5	c.376+3470C>T		intron_variant		3		ENSP00000451785.1
UBR7	ENST00000555329.1	c.54+16C>T		intron_variant		4		ENSP00000452488.1
UBR7	ENST00000553674.1	n.*511+16C>T		intron_variant		2		ENSP00000450470.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16510 AN: 151854 Hom.: 945 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.117

GnomAD3 exomes AF: 0.104 AC: 25909 AN: 248686 Hom.: 1424 AF XY: 0.104 AC XY: 14097 AN XY: 134908

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.107

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0872

Gnomad NFE exome AF: 0.0924

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0955 AC: 139106 AN: 1457022 Hom.: 6974 Cov.: 32 AF XY: 0.0962 AC XY: 69611 AN XY: 723968

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.0874

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0861

Gnomad4 NFE exome AF: 0.0905

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.109 AC: 16555 AN: 151972 Hom.: 953 Cov.: 32 AF XY: 0.108 AC XY: 8049 AN XY: 74292

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.117

Alfa AF: 0.108 Hom.: 300

Bravo AF: 0.112

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17128941; hg19: chr14-93685097; COSMIC: COSV50149023; COSMIC: COSV50149023;