Variant 22-24495324-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000382760.2(UPB1):c.-80C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,467,332 control chromosomes in the GnomAD database, including 252,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27783 hom., cov: 34)

Exomes 𝑓: 0.58 ( 224426 hom. )

Consequence

UPB1
ENST00000382760.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.981

Variant links:

Genes affected

UPB1 (HGNC:16297): (beta-ureidopropionase 1) This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity. [provided by RefSeq, Jul 2008]

UPB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-24495324-C-G is Benign according to our data. Variant chr22-24495324-C-G is described in ClinVar as [Benign]. Clinvar id is 100154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPB1	NM_016327.3 linkuse as main transcript			upstream_gene_variant		ENST00000326010.10	NP_057411.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
UPB1	ENST00000382760.2 linkuse as main transcript	c.-80C>G	5_prime_UTR_variant	1/4	5		ENSP00000372208
UPB1	ENST00000415388.5 linkuse as main transcript	c.-80C>G	5_prime_UTR_variant, NMD_transcript_variant	1/9	5		ENSP00000400684
UPB1	ENST00000326010.10 linkuse as main transcript		upstream_gene_variant		1	NM_016327.3	ENSP00000324343	P1

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91151

AN:

152034

Hom.:

27732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.580

AC:

762792

AN:

1315180

Hom.:

224426

Cov.:

AF XY:

0.572

AC XY:

378879

AN XY:

661802

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.501

Gnomad4 SAS exome

AF:

0.360

Gnomad4 FIN exome

AF:

0.561

Gnomad4 NFE exome

AF:

0.598

Gnomad4 OTH exome

AF:

0.578

GnomAD4 genome

AF:

0.600

AC:

91262

AN:

152152

Hom.:

27783

Cov.:

AF XY:

0.593

AC XY:

44136

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.663

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.491

Gnomad4 SAS

AF:

0.347

Gnomad4 FIN

AF:

0.559

Gnomad4 NFE

AF:

0.595

Gnomad4 OTH

AF:

0.608

Alfa

AF:

0.607

Hom.:

2665

Bravo

AF:

0.615

Asia WGS

AF:

0.418

AC:

1453

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	literature only	Diasio Lab, Mayo Clinic	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Deficiency of beta-ureidopropionase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.14

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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