rs13948

Positions:

• chr1-45015157-T-C

Variant summary

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

The ENST00000246337.9(UROD):​c.942+151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,437,164 control chromosomes in the GnomAD database, including 47,548 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 0.23 (4509 hom., cov: 33)
  • Exomes 𝑓: 0.25 (43039 hom.)
• Consequence: UROD ENST00000246337.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

Genes affected

UROD (HGNC:12591): (uroporphyrinogen decarboxylase) This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROD	NM_000374.5	c.942+151T>C		intron_variant		ENST00000246337.9	NP_000365.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UROD	ENST00000246337.9	c.942+151T>C		intron_variant		1	NM_000374.5	ENSP00000246337	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35657 AN: 152078 Hom.: 4503 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.255 AC: 327040 AN: 1284968 Hom.: 43039 Cov.: 20 AF XY: 0.254 AC XY: 162714 AN XY: 640322

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.234 AC: 35675 AN: 152196 Hom.: 4509 Cov.: 33 AF XY: 0.235 AC XY: 17454 AN XY: 74388

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.242

Alfa AF: 0.244 Hom.: 4625

Bravo AF: 0.239

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs13948; hg19: chr1-45480829; COSMIC: COSV55798954; COSMIC: COSV55798954;