dbSNP rs2232861: UPB1:n.-218G>A (chr22-24495186-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000415388.5(UPB1):n.-218G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 612,180 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.020 ( 51 hom., cov: 33)

Exomes 𝑓: 0.0086 ( 37 hom. )

Consequence

UPB1
ENST00000415388.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

6 publications found

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:

ADORA2A-AS1 (HGNC:37122): (ADORA2A antisense RNA 1)

ADORA2A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0196 (2986/152360) while in subpopulation AFR AF = 0.0514 (2138/41578). AF 95% confidence interval is 0.0496. There are 51 homozygotes in GnomAd4. There are 1460 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPB1	NM_016327.3 link	c.-218G>A		upstream_gene_variant		ENST00000326010.10	NP_057411.1	Q9UBR1A0A024R1H3B3KNC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPB1	ENST00000326010.10 link	c.-218G>A		upstream_gene_variant		1	NM_016327.3	ENSP00000324343.5		Q9UBR1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2977

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00702

Gnomad OTH

AF:

0.00907

GnomAD4 exome

AF:

0.00856

AC:

3937

AN:

459820

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

2056

AN XY:

242724

show subpopulations

African (AFR)

AF:

0.0497

AC:

668

AN:

13448

American (AMR)

AF:

0.00405

AC:

106

AN:

26198

Ashkenazi Jewish (ASJ)

AF:

0.000408

AC:

AN:

14698

East Asian (EAS)

AF:

0.00132

AC:

AN:

30332

South Asian (SAS)

AF:

0.0109

AC:

545

AN:

50078

European-Finnish (FIN)

AF:

0.0179

AC:

516

AN:

28872

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

2002

European-Non Finnish (NFE)

AF:

0.00657

AC:

1760

AN:

267996

Other (OTH)

AF:

0.0105

AC:

274

AN:

26196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

195

391

586

782

977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0196

AC:

2986

AN:

152360

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1460

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0514

AC:

2138

AN:

41578

American (AMR)

AF:

0.00640

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00309

AC:

AN:

5186

South Asian (SAS)

AF:

0.0126

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0163

AC:

173

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00704

AC:

479

AN:

68038

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

151

302

454

605

756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00671

Hom.:

Bravo

AF:

0.0194

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.0

(source)

DANN

Benign

0.95

PhyloP100

0.23

PromoterAI

0.53

Over-expression

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over