Variant 15-42945374-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_174916.3(UBR1):c.5205A>G(p.Gln1735=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,614,116 control chromosomes in the GnomAD database, including 1,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 396 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1553 hom. )

Consequence

UBR1
NM_174916.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.379

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 15-42945374-T-C is Benign according to our data. Variant chr15-42945374-T-C is described in ClinVar as [Benign]. Clinvar id is 262897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.379 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 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.5205A>G	p.Gln1735=	synonymous_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.5205A>G	p.Gln1735=	synonymous_variant	47/47	1	NM_174916.3	P1	Q8IWV7-1
UBR1	ENST00000562173.1 linkuse as main transcript	n.410A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9227

AN:

152142

Hom.:

394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0515

Gnomad ASJ

AF:

0.0858

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0823

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0476

AC:

11960

AN:

251446

Hom.:

415

AF XY:

0.0481

AC XY:

6535

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.0371

Gnomad ASJ exome

AF:

0.0839

Gnomad EAS exome

AF:

0.0589

Gnomad SAS exome

AF:

0.0795

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.0323

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0386

AC:

56396

AN:

1461856

Hom.:

1553

Cov.:

AF XY:

0.0399

AC XY:

29006

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.0374

Gnomad4 ASJ exome

AF:

0.0822

Gnomad4 EAS exome

AF:

0.0840

Gnomad4 SAS exome

AF:

0.0790

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0488

GnomAD4 genome

AF:

0.0607

AC:

9239

AN:

152260

Hom.:

396

Cov.:

AF XY:

0.0610

AC XY:

4539

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0515

Gnomad4 ASJ

AF:

0.0858

Gnomad4 EAS

AF:

0.0615

Gnomad4 SAS

AF:

0.0824

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0307

Gnomad4 OTH

AF:

0.0535

Alfa

AF:

0.0440

Hom.:

286

Bravo

AF:

0.0642

Asia WGS

AF:

0.0830

AC:

288

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.1

DANN

Benign

0.54

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