rs1799388

Positions:

• chr3-126506304-T-C
• chr3-126506304-T-G

Variant summary

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

The NM_144639.3(UROC1):​c.603-293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,162 control chromosomes in the GnomAD database, including 60,688 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 0.89 (60688 hom., cov: 31)
• Consequence: UROC1 NM_144639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

Genes affected

UROC1 (HGNC:26444): (urocanate hydratase 1) This gene encodes an enzyme involved in the second step of histidine catabolism, metabolizing urocanic acid to formiminoglutamic acid. Deficiency of this enzyme results in urocanic aciduria, and is an apparent cause of mental retardation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROC1	NM_144639.3	c.603-293A>G		intron_variant		ENST00000290868.7	NP_653240.1
UROC1	NM_001165974.2	c.603-293A>G		intron_variant			NP_001159446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UROC1	ENST00000290868.7	c.603-293A>G		intron_variant		1	NM_144639.3	ENSP00000290868	P1
UROC1	ENST00000383579.3	c.603-293A>G		intron_variant		1		ENSP00000373073

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135409 AN: 152044 Hom.: 60656 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 135495 AN: 152162 Hom.: 60688 Cov.: 31 AF XY: 0.894 AC XY: 66528 AN XY: 74392

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.935

Gnomad4 OTH AF: 0.899

Alfa AF: 0.927 Hom.: 131946

Bravo AF: 0.885

Asia WGS AF: 0.900 AC: 3131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.25

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: rs1799388; hg19: chr3-126225147;