rs2232861

Positions:

• chr22-24495186-G-A
• chr22-24495186-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000415388.5(UPB1):​c.-218G>A variant causes a 5 prime UTR, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPB1	ENST00000415388.5	c.-218G>A		5_prime_UTR_variant, NMD_transcript_variant	1/9	5

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2977 AN: 152242 Hom.: 51 Cov.: 33

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.: 37 Cov.: 3 AF XY: 0.00847 AC XY: 2056 AN XY: 242724

Gnomad4 AFR exome AF: 0.0497

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.000408

Gnomad4 EAS exome AF: 0.00132

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.0179

Gnomad4 NFE exome AF: 0.00657

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0196 AC: 2986 AN: 152360 Hom.: 51 Cov.: 33 AF XY: 0.0196 AC XY: 1460 AN XY: 74510

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.00640

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.00704

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00671 Hom.: 1

Bravo AF: 0.0194

Asia WGS AF: 0.0110 AC: 40 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
DANN	Benign	0.95

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

Other links and lift over

dbSNP: rs2232861; hg19: chr22-24891154;