rs2232861

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• 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: 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

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>A		upstream_gene	N/A	NP_057411.1	Q9UBR1
	ADORA2A-AS1	NR_028483.2		n.-112C>T		upstream_gene	N/A
	ADORA2A-AS1	NR_028484.3		n.-112C>T		upstream_gene	N/A

Ensembl Transcripts

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

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

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: 6 AN: 14698

East Asian (EAS) AF: 0.00132 AC: 40 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: 22 AN: 2002

European-Non Finnish (NFE) AF: 0.00657 AC: 1760 AN: 267996

Other (OTH) AF: 0.0105 AC: 274 AN: 26196

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

African (AFR) AF: 0.0514 AC: 2138 AN: 41578

American (AMR) AF: 0.00640 AC: 98 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5186

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4830

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00704 AC: 479 AN: 68038

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.0
DANN	Benign	0.95
PhyloP100		0.23
PromoterAI		0.53	Over-expression
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs2232861; hg19: chr22-24891154;