rs2070475

Variant names:

• chr22-24495387-A-T
• rs2070475
• NM_016327.3:c.-17A>T

Your query was ambiguous. Multiple possible variants found:

• chr22-24495387-A-T
• chr22-24495387-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016327.3(UPB1):​c.-17A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,612,114 control chromosomes in the GnomAD database, including 20,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1399 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19455 hom.)
• Consequence: UPB1 NM_016327.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -4.86
• Publications: 13 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]

UPB1 Gene-Disease associations (from GenCC):

• beta-ureidopropionase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-24495387-A-T is Benign according to our data. Variant chr22-24495387-A-T is described in ClinVar as Benign. ClinVar VariationId is 100155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016327.3. 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.-17A>T		5_prime_UTR	Exon 1 of 10	NP_057411.1	Q9UBR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPB1	ENST00000326010.10	TSL:1 MANE Select	c.-17A>T		5_prime_UTR	Exon 1 of 10	ENSP00000324343.5	Q9UBR1
	UPB1	ENST00000858218.1		c.-17A>T		5_prime_UTR	Exon 1 of 11	ENSP00000528277.1
	UPB1	ENST00000858215.1		c.-17A>T		5_prime_UTR	Exon 1 of 11	ENSP00000528274.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18213 AN: 152182 Hom.: 1399 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.151 AC: 37600 AN: 248926 AF XY: 0.154

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0651

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.159 AC: 232483 AN: 1459814 Hom.: 19455 Cov.: 33 AF XY: 0.160 AC XY: 116444 AN XY: 726304

African (AFR) AF: 0.0210 AC: 704 AN: 33472

American (AMR) AF: 0.108 AC: 4823 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 1619 AN: 26134

East Asian (EAS) AF: 0.261 AC: 10364 AN: 39698

South Asian (SAS) AF: 0.184 AC: 15844 AN: 86248

European-Finnish (FIN) AF: 0.173 AC: 8914 AN: 51620

Middle Eastern (MID) AF: 0.0583 AC: 335 AN: 5748

European-Non Finnish (NFE) AF: 0.163 AC: 180846 AN: 1111792

Other (OTH) AF: 0.150 AC: 9034 AN: 60380

GnomAD4 genome AF: 0.120 AC: 18208 AN: 152300 Hom.: 1399 Cov.: 32 AF XY: 0.121 AC XY: 9020 AN XY: 74466

African (AFR) AF: 0.0305 AC: 1267 AN: 41594

American (AMR) AF: 0.105 AC: 1612 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1498 AN: 5156

South Asian (SAS) AF: 0.177 AC: 857 AN: 4830

European-Finnish (FIN) AF: 0.164 AC: 1744 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10687 AN: 68014

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.126 Hom.: 253

Bravo AF: 0.108

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of beta-ureidopropionase (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.50
PhyloP100		-4.9
PromoterAI		0.10	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs2070475; hg19: chr22-24891355; COSMIC: COSV58113975; COSMIC: COSV58113975;