rs4679251

Variant names:

• chr3-126503241-G-A
• rs4679251
• NM_144639.3:c.902+754C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

UROC1 Gene-Disease associations (from GenCC):

• urocanic aciduria

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROC1	NM_144639.3	MANE Select	c.902+754C>T		intron	N/A	NP_653240.1
	UROC1	NM_001165974.2		c.902+754C>T		intron	N/A	NP_001159446.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROC1	ENST00000290868.7	TSL:1 MANE Select	c.902+754C>T		intron	N/A	ENSP00000290868.2
	UROC1	ENST00000383579.3	TSL:1	c.902+754C>T		intron	N/A	ENSP00000373073.3

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

African (AFR) AF: 0.451 AC: 18709 AN: 41472

American (AMR) AF: 0.531 AC: 8127 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2090 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2871 AN: 5162

South Asian (SAS) AF: 0.615 AC: 2970 AN: 4832

European-Finnish (FIN) AF: 0.512 AC: 5414 AN: 10574

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38729 AN: 67968

Other (OTH) AF: 0.527 AC: 1112 AN: 2112

Alfa AF: 0.557 Hom.: 31383

Bravo AF: 0.527

Asia WGS AF: 0.530 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.87
DANN	Benign	0.71
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs4679251; hg19: chr3-126222084;