1-45012214-C-A
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The ENST00000652287(UROD):c.-52C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,612,690 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 3 hom. )
Consequence
UROD
ENST00000652287 5_prime_UTR
ENST00000652287 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.314
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00127 (193/152256) while in subpopulation NFE AF= 0.00251 (171/68016). AF 95% confidence interval is 0.00221. There are 0 homozygotes in gnomad4. There are 92 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 3 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UROD | NM_000374.5 | c.-52C>A | upstream_gene_variant | ENST00000246337.9 | NP_000365.3 | |||
UROD | NR_036510.2 | n.-40C>A | upstream_gene_variant | |||||
UROD | NR_158184.1 | n.-40C>A | upstream_gene_variant | |||||
UROD | NR_158185.1 | n.-40C>A | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00127 AC: 193AN: 152138Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000970 AC: 244AN: 251434Hom.: 0 AF XY: 0.000898 AC XY: 122AN XY: 135906
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GnomAD4 exome AF: 0.00200 AC: 2915AN: 1460434Hom.: 3 Cov.: 31 AF XY: 0.00187 AC XY: 1355AN XY: 726526
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GnomAD4 genome AF: 0.00127 AC: 193AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92AN XY: 74442
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Porphyria cutanea tarda Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at