Genetic Variant UROD:c.-136+47T>G (chr1-45012132-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000652165.1(UROD):c.-136+47T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,316,932 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 264 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 223 hom. )

Consequence

UROD
ENST00000652165.1 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.61

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-45012132-T-G is Benign according to our data. Variant chr1-45012132-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 368874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
UROD	NM_000374.5 link	c.-134T>G	upstream_gene_variant	ENST00000246337.9	NP_000365.3	P06132
UROD	NR_036510.2 link	n.-122T>G	upstream_gene_variant
UROD	NR_158184.1 link	n.-122T>G	upstream_gene_variant
UROD	NR_158185.1 link	n.-122T>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROD	ENST00000246337.9 link	c.-134T>G		upstream_gene_variant		1	NM_000374.5	ENSP00000246337.4		P06132

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

5101

AN:

152040

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.00857

AC:

2010

AN:

234542

Hom.:

118

AF XY:

0.00621

AC XY:

790

AN XY:

127114

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.00633

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000237

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000576

Gnomad OTH exome

AF:

0.00429

GnomAD4 exome

AF:

0.00380

AC:

4430

AN:

1164774

Hom.:

223

Cov.:

AF XY:

0.00327

AC XY:

1934

AN XY:

592316

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.00698

Gnomad4 ASJ exome

AF:

0.0000415

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000189

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000389

Gnomad4 OTH exome

AF:

0.00908

GnomAD4 genome

AF:

0.0336

AC:

5114

AN:

152158

Hom.:

264

Cov.:

AF XY:

0.0324

AC XY:

2411

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Porphyria cutanea tarda

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.091

DANN

Benign

0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over