22-24500046-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016327.3(UPB1):c.105-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,609,820 control chromosomes in the GnomAD database, including 1,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.037 (185 hom., cov: 33)
  • Exomes 𝑓: 0.026 (1156 hom.)
• Consequence: UPB1 NM_016327.3 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.674

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPB1	NM_016327.3	c.105-61A>G		intron_variant		ENST00000326010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPB1	ENST00000326010.10	c.105-61A>G		intron_variant		1	NM_016327.3	P1
UPB1	ENST00000382760.2	c.105-61A>G		intron_variant		5
UPB1	ENST00000415388.5	c.105-2080A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5590 AN: 152084 Hom.: 184 Cov.: 33

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0258 AC: 37618 AN: 1457618 Hom.: 1156 AF XY: 0.0273 AC XY: 19796 AN XY: 725418

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.0619

Gnomad4 ASJ exome AF: 0.0378

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0966

Gnomad4 FIN exome AF: 0.00900

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0302

GnomAD4 genome AF: 0.0368 AC: 5608 AN: 152202 Hom.: 185 Cov.: 33 AF XY: 0.0378 AC XY: 2816 AN XY: 74406

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.0910

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0235 Hom.: 7

Bravo AF: 0.0396

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Diasio Lab, Mayo Clinic

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.96
Dann	Benign	0.62

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: rs2232865; hg19: chr22-24896014; COSMIC: COSV58116217; COSMIC: COSV58116217;