rs2228084
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000374.5(UROD):āc.603A>Gā(p.Pro201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,614,134 control chromosomes in the GnomAD database, including 4,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.086 ( 730 hom., cov: 32)
Exomes š: 0.064 ( 3344 hom. )
Consequence
UROD
NM_000374.5 synonymous
NM_000374.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.440
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 1-45014037-A-G is Benign according to our data. Variant chr1-45014037-A-G is described in ClinVar as [Benign]. Clinvar id is 255961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45014037-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.44 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UROD | NM_000374.5 | c.603A>G | p.Pro201= | synonymous_variant | 6/10 | ENST00000246337.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UROD | ENST00000246337.9 | c.603A>G | p.Pro201= | synonymous_variant | 6/10 | 1 | NM_000374.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0862 AC: 13111AN: 152128Hom.: 723 Cov.: 32
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GnomAD3 exomes AF: 0.0758 AC: 19068AN: 251476Hom.: 911 AF XY: 0.0710 AC XY: 9653AN XY: 135916
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GnomAD4 exome AF: 0.0639 AC: 93456AN: 1461888Hom.: 3344 Cov.: 34 AF XY: 0.0627 AC XY: 45597AN XY: 727246
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GnomAD4 genome ? AF: 0.0864 AC: 13154AN: 152246Hom.: 730 Cov.: 32 AF XY: 0.0870 AC XY: 6475AN XY: 74422
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Familial porphyria cutanea tarda Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at