dbSNP rs13948: UROD:c.942+151T>C (chr1-45015157-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.669

Publications

10 publications found

Variant links:

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

UROD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROD	NM_000374.5 link	c.942+151T>C		intron_variant	Intron 9 of 9	ENST00000246337.9	NP_000365.3	P06132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROD	ENST00000246337.9 link	c.942+151T>C		intron_variant	Intron 9 of 9	1	NM_000374.5	ENSP00000246337.4		P06132

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35657

AN:

152078

Hom.:

4503

Cov.:

show subpopulations

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.:

AF XY:

0.254

AC XY:

162714

AN XY:

640322

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13285

26570

39854

53139

66424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8122

16244

24366

32488

40610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.234

AC:

35675

AN:

152196

Hom.:

4509

Cov.:

AF XY:

0.235

AC XY:

17454

AN XY:

74388

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.249

AC:

16952

AN:

67980

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1389

2778

4167

5556

6945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

(source)

DANN

Benign

0.69

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over