22-24495186-G-T

Variant names:

• chr22-24495186-G-T
• rs2232861
• ENST00000415388.5:n.-218G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000415388.5(UPB1):​n.-218G>T 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 0.00000435 in 459,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: UPB1 ENST00000415388.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 6 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415388.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPB1	NM_016327.3	MANE Select	c.-218G>T		upstream_gene	N/A	NP_057411.1	Q9UBR1
	ADORA2A-AS1	NR_028483.2		n.-112C>A		upstream_gene	N/A
	ADORA2A-AS1	NR_028484.3		n.-112C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPB1	ENST00000415388.5	TSL:5	n.-218G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000400684.1	F8WC94
	UPB1	ENST00000415388.5	TSL:5	n.-218G>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000400684.1	F8WC94
	UPB1	ENST00000415388.5	TSL:5	n.-218G>T		5_prime_UTR	Exon 1 of 9	ENSP00000400684.1	F8WC94

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000435 AC: 2 AN: 459842 Hom.: 0 Cov.: 3 AF XY: 0.00000412 AC XY: 1 AN XY: 242734

African (AFR) AF: 0.00 AC: 0 AN: 13450

American (AMR) AF: 0.0000382 AC: 1 AN: 26200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14698

East Asian (EAS) AF: 0.00 AC: 0 AN: 30332

South Asian (SAS) AF: 0.0000200 AC: 1 AN: 50078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 268010

Other (OTH) AF: 0.00 AC: 0 AN: 26200

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.87
PhyloP100		0.23
PromoterAI		0.91	Over-expression

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2232861;

hg19: chr22-24891154;