rs4679251

chr3-126503241-G-A

Variant summary

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

The NM_144639.3(UROC1):c.902+754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,092 control chromosomes in the GnomAD database, including 21,767 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 0.53 (21767 hom., cov: 34)
• Consequence: UROC1 NM_144639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROC1	NM_144639.3	c.902+754C>T		intron_variant		ENST00000290868.7
UROC1	NM_001165974.2	c.902+754C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROC1	ENST00000290868.7	c.902+754C>T		intron_variant		1	NM_144639.3	P1
UROC1	ENST00000383579.3	c.902+754C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80735 AN: 151974 Hom.: 21751 Cov.: 34

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.531 AC: 80775 AN: 152092 Hom.: 21767 Cov.: 34 AF XY: 0.534 AC XY: 39715 AN XY: 74354

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.527

Alfa AF: 0.562 Hom.: 24520

Bravo AF: 0.527

Asia WGS AF: 0.530 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.87
Dann	Benign	0.71

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: rs4679251; hg19: chr3-126222084;