Variant chr15-42945216-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_174916.3(UBR1):c.*113G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,415,250 control chromosomes in the GnomAD database, including 4,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 363 hom., cov: 33)

Exomes 𝑓: 0.079 ( 4579 hom. )

Consequence

UBR1
NM_174916.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.174

Variant links:

Genes affected

UBR1 (HGNC:16808): (ubiquitin protein ligase E3 component n-recognin 1) The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

UBR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 15-42945216-C-T is Benign according to our data. Variant chr15-42945216-C-T is described in ClinVar as [Benign]. Clinvar id is 1281511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR1	NM_174916.3 linkuse as main transcript	c.*113G>A		3_prime_UTR_variant	47/47	ENST00000290650.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR1	ENST00000290650.9 linkuse as main transcript	c.*113G>A		3_prime_UTR_variant	47/47	1	NM_174916.3	P1	Q8IWV7-1
UBR1	ENST00000562173.1 linkuse as main transcript	n.568G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

9350

AN:

152166

Hom.:

363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.0833

Gnomad ASJ

AF:

0.0855

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0907

Gnomad OTH

AF:

0.0699

GnomAD4 exome

AF:

0.0789

AC:

99704

AN:

1262966

Hom.:

4579

Cov.:

AF XY:

0.0775

AC XY:

49174

AN XY:

634234

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.0677

Gnomad4 ASJ exome

AF:

0.0811

Gnomad4 EAS exome

AF:

0.000268

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.0258

Gnomad4 NFE exome

AF:

0.0920

Gnomad4 OTH exome

AF:

0.0774

GnomAD4 genome

AF:

0.0614

AC:

9346

AN:

152284

Hom.:

363

Cov.:

AF XY:

0.0576

AC XY:

4290

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.0831

Gnomad4 ASJ

AF:

0.0855

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.0907

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0775

Hom.:

129

Bravo

AF:

0.0651

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.3

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over