14-93218751-C-T

Variant names:

• chr14-93218751-C-T
• rs17128941
• NM_175748.4:c.810+16C>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.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
• Publications: 5 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

ENSG00000259066 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	NM_175748.4	MANE Select	c.810+16C>T		intron	N/A	NP_786924.2
	UBR7	NR_038150.2		n.712+16C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	ENST00000013070.11	TSL:1 MANE Select	c.810+16C>T		intron	N/A	ENSP00000013070.6
	UBR7	ENST00000966805.1		c.843+16C>T		intron	N/A	ENSP00000636864.1
	UBR7	ENST00000940497.1		c.822+4C>T		splice_region intron	N/A	ENSP00000610556.1

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

GnomAD2 exomes AF: 0.104 AC: 25909 AN: 248686 AF XY: 0.104

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 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

African (AFR) AF: 0.142 AC: 4733 AN: 33334

American (AMR) AF: 0.115 AC: 5145 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3576 AN: 26002

East Asian (EAS) AF: 0.0874 AC: 3460 AN: 39600

South Asian (SAS) AF: 0.118 AC: 10171 AN: 86080

European-Finnish (FIN) AF: 0.0861 AC: 4581 AN: 53204

Middle Eastern (MID) AF: 0.153 AC: 878 AN: 5748

European-Non Finnish (NFE) AF: 0.0905 AC: 100265 AN: 1108316

Other (OTH) AF: 0.105 AC: 6297 AN: 60172

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

African (AFR) AF: 0.142 AC: 5873 AN: 41436

American (AMR) AF: 0.107 AC: 1629 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3470

East Asian (EAS) AF: 0.109 AC: 563 AN: 5164

South Asian (SAS) AF: 0.114 AC: 546 AN: 4802

European-Finnish (FIN) AF: 0.0779 AC: 822 AN: 10556

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6233 AN: 67980

Other (OTH) AF: 0.117 AC: 246 AN: 2106

Alfa AF: 0.109 Hom.: 307

Bravo AF: 0.112

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.82
PhyloP100		-1.1
PromoterAI		-0.0012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17128941; hg19: chr14-93685097; COSMIC: COSV50149023; COSMIC: COSV50149023;