chr1-45012890-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_000374.5(UROD):c.21-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,613,514 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
UROD
NM_000374.5 splice_polypyrimidine_tract, intron
NM_000374.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.103
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 -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 1-45012890-C-T is Benign according to our data. Variant chr1-45012890-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2183641.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000118 (172/1461262) while in subpopulation MID AF= 0.00538 (31/5764). AF 95% confidence interval is 0.00389. There are 1 homozygotes in gnomad4_exome. There are 99 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UROD | NM_000374.5 | c.21-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000246337.9 | |||
UROD | NR_036510.2 | n.66C>T | non_coding_transcript_exon_variant | 2/10 | |||
UROD | NR_158184.1 | n.66C>T | non_coding_transcript_exon_variant | 2/10 | |||
UROD | NR_158185.1 | n.33-17C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UROD | ENST00000246337.9 | c.21-17C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000374.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000224 AC: 56AN: 250028Hom.: 1 AF XY: 0.000259 AC XY: 35AN XY: 135364
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GnomAD4 exome AF: 0.000118 AC: 172AN: 1461262Hom.: 1 Cov.: 32 AF XY: 0.000136 AC XY: 99AN XY: 726946
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74428
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
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