Variant 15-42963923-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_174916.3(UBR1):c.4700+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,566,924 control chromosomes in the GnomAD database, including 599,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 55974 hom., cov: 29)

Exomes 𝑓: 0.88 ( 543567 hom. )

Consequence

UBR1
NM_174916.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.53

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 15-42963923-T-C is Benign according to our data. Variant chr15-42963923-T-C is described in ClinVar as [Benign]. Clinvar id is 262895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42963923-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR1	NM_174916.3 linkuse as main transcript	c.4700+12A>G		intron_variant		ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9 linkuse as main transcript	c.4700+12A>G		intron_variant		1	NM_174916.3	ENSP00000290650.4		Q8IWV7-1

Frequencies

GnomAD3 genomes

AF:

0.858

AC:

130231

AN:

151832

Hom.:

55946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.802

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.860

Gnomad ASJ

AF:

0.906

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.886

Gnomad FIN

AF:

0.873

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.887

Gnomad OTH

AF:

0.870

GnomAD3 exomes

AF:

0.864

AC:

216794

AN:

250914

Hom.:

93851

AF XY:

0.869

AC XY:

117868

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.803

Gnomad AMR exome

AF:

0.832

Gnomad ASJ exome

AF:

0.901

Gnomad EAS exome

AF:

0.798

Gnomad SAS exome

AF:

0.882

Gnomad FIN exome

AF:

0.871

Gnomad NFE exome

AF:

0.882

Gnomad OTH exome

AF:

0.890

GnomAD4 exome

AF:

0.876

AC:

1239461

AN:

1414974

Hom.:

543567

Cov.:

AF XY:

0.877

AC XY:

620320

AN XY:

707116

show subpopulations

Gnomad4 AFR exome

AF:

0.792

Gnomad4 AMR exome

AF:

0.838

Gnomad4 ASJ exome

AF:

0.902

Gnomad4 EAS exome

AF:

0.799

Gnomad4 SAS exome

AF:

0.882

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.882

Gnomad4 OTH exome

AF:

0.880

GnomAD4 genome

AF:

0.858

AC:

130311

AN:

151950

Hom.:

55974

Cov.:

AF XY:

0.857

AC XY:

63646

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.802

Gnomad4 AMR

AF:

0.860

Gnomad4 ASJ

AF:

0.906

Gnomad4 EAS

AF:

0.816

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.873

Gnomad4 NFE

AF:

0.887

Gnomad4 OTH

AF:

0.864

Alfa

AF:

0.877

Hom.:

6381

Bravo

AF:

0.852

Asia WGS

AF:

0.826

AC:

2871

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Johanson-Blizzard syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.53

Position offset: 1

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