NM_000374.5:c.942+151T>C

Variant names:

• chr1-45015157-T-C
• rs13948
• NM_000374.5:c.942+151T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000374.5(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 NM_000374.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 10 publications found

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]

UROD Gene-Disease associations (from GenCC):

• UROD-related inherited porphyria

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• familial porphyria cutanea tarda

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• hepatoerythropoietic porphyria

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000374.5. 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
	UROD	NM_000374.5	MANE Select	c.942+151T>C		intron	N/A	NP_000365.3
	UROD	NR_036510.2		n.1004+151T>C		intron	N/A
	UROD	NR_158184.1		n.1023+151T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROD	ENST00000246337.9	TSL:1 MANE Select	c.942+151T>C		intron	N/A	ENSP00000246337.4	P06132
	UROD	ENST00000894914.1		c.966+151T>C		intron	N/A	ENSP00000564973.1
	UROD	ENST00000894916.1		c.957+151T>C		intron	N/A	ENSP00000564975.1

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

African (AFR) AF: 0.164 AC: 4796 AN: 29304

American (AMR) AF: 0.375 AC: 13367 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6365 AN: 24380

East Asian (EAS) AF: 0.291 AC: 10378 AN: 35608

South Asian (SAS) AF: 0.257 AC: 20045 AN: 77900

European-Finnish (FIN) AF: 0.243 AC: 11771 AN: 48406

Middle Eastern (MID) AF: 0.213 AC: 818 AN: 3840

European-Non Finnish (NFE) AF: 0.252 AC: 245582 AN: 975622

Other (OTH) AF: 0.257 AC: 13918 AN: 54240

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

African (AFR) AF: 0.165 AC: 6871 AN: 41544

American (AMR) AF: 0.330 AC: 5041 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3468

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5182

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4826

European-Finnish (FIN) AF: 0.228 AC: 2410 AN: 10588

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16952 AN: 67980

Other (OTH) AF: 0.242 AC: 511 AN: 2112

Alfa AF: 0.244 Hom.: 5823

Bravo AF: 0.239

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.69
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13948; hg19: chr1-45480829; COSMIC: COSV55798954; COSMIC: COSV55798954;