rs1805312
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The ENST00000409155.8(ALAD):c.398-34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 1,607,220 control chromosomes in the GnomAD database, including 7,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.079 ( 810 hom., cov: 33)
Exomes 𝑓: 0.086 ( 7139 hom. )
Consequence
ALAD
ENST00000409155.8 intron
ENST00000409155.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.27
Genes affected
ALAD (HGNC:395): (aminolevulinate dehydratase) The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 9-113390710-C-G is Benign according to our data. Variant chr9-113390710-C-G is described in ClinVar as [Benign]. Clinvar id is 1178261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALAD | NM_000031.6 | c.398-34G>C | intron_variant | ENST00000409155.8 | NP_000022.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALAD | ENST00000409155.8 | c.398-34G>C | intron_variant | 1 | NM_000031.6 | ENSP00000386284 | P1 | |||
ALAD | ENST00000464749.5 | n.481G>C | non_coding_transcript_exon_variant | 3/3 | 4 | |||||
ALAD | ENST00000468504.5 | n.607G>C | non_coding_transcript_exon_variant | 5/7 | 5 | |||||
ALAD | ENST00000482847.5 | n.671-34G>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0786 AC: 11965AN: 152140Hom.: 801 Cov.: 33
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GnomAD3 exomes AF: 0.114 AC: 26537AN: 233556Hom.: 2680 AF XY: 0.105 AC XY: 13317AN XY: 126626
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GnomAD4 exome AF: 0.0856 AC: 124614AN: 1454962Hom.: 7139 Cov.: 35 AF XY: 0.0848 AC XY: 61355AN XY: 723378
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GnomAD4 genome AF: 0.0787 AC: 11986AN: 152258Hom.: 810 Cov.: 33 AF XY: 0.0815 AC XY: 6065AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
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
DS_AG_spliceai
Position offset: -19
Find out detailed SpliceAI scores and Pangolin per-transcript scores at