Variant 22-24495387-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016327.3(UPB1):c.-17A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,612,114 control chromosomes in the GnomAD database, including 20,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1399 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19455 hom. )

Consequence

UPB1
NM_016327.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -4.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 22-24495387-A-T is Benign according to our data. Variant chr22-24495387-A-T is described in ClinVar as [Benign]. Clinvar id is 100155.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPB1	NM_016327.3 linkuse as main transcript	c.-17A>T		5_prime_UTR_variant	1/10	ENST00000326010.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
UPB1	ENST00000326010.10 linkuse as main transcript	c.-17A>T	5_prime_UTR_variant	1/10	1	NM_016327.3	P1
UPB1	ENST00000382760.2 linkuse as main transcript	c.-17A>T	5_prime_UTR_variant	1/4	5
UPB1	ENST00000415388.5 linkuse as main transcript	c.-17A>T	5_prime_UTR_variant, NMD_transcript_variant	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18213

AN:

152182

Hom.:

1399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0688

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.151

AC:

37600

AN:

248926

Hom.:

3254

AF XY:

0.154

AC XY:

20804

AN XY:

134840

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.0651

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.159

AC:

232483

AN:

1459814

Hom.:

19455

Cov.:

AF XY:

0.160

AC XY:

116444

AN XY:

726304

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.0619

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.120

AC:

18208

AN:

152300

Hom.:

1399

Cov.:

AF XY:

0.121

AC XY:

9020

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0305

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0688

Gnomad4 EAS

AF:

0.291

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.126

Hom.:

253

Bravo

AF:

0.108

Asia WGS

AF:

0.206

AC:

718

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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. -

not provided

Other:1

not provided, no classification provided

literature only

Diasio Lab, Mayo Clinic

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.10

DANN

Benign

0.50

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