11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTT
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The NM_000190.4(HMBS):c.33+133_33+135delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 710,748 control chromosomes in the GnomAD database, including 1,849 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.24 ( 839 hom., cov: 0)
Exomes 𝑓: 0.14 ( 1849 hom. )
Failed GnomAD Quality Control
Consequence
HMBS
NM_000190.4 intron
NM_000190.4 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.83
Genes affected
HMBS (HGNC:4982): (hydroxymethylbilane synthase) This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BA1
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 15667AN: 64316Hom.: 838 Cov.: 0 FAILED QC
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GnomAD4 exome AF: 0.144 AC: 102378AN: 710748Hom.: 1849 AF XY: 0.142 AC XY: 49823AN XY: 350610
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.244 AC: 15671AN: 64348Hom.: 839 Cov.: 0 AF XY: 0.237 AC XY: 6760AN XY: 28548
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Not reported inComputational scores
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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