rs352167
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000688.6(ALAS1):c.578-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,487,906 control chromosomes in the GnomAD database, including 203,634 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.50 ( 19313 hom., cov: 34)
Exomes 𝑓: 0.52 ( 184321 hom. )
Consequence
ALAS1
NM_000688.6 intron
NM_000688.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.74
Genes affected
ALAS1 (HGNC:396): (5'-aminolevulinate synthase 1) This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALAS1 | NM_000688.6 | c.578-53T>C | intron_variant | ENST00000484952.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALAS1 | ENST00000484952.6 | c.578-53T>C | intron_variant | 1 | NM_000688.6 | P1 | |||
ALAS1 | ENST00000310271.6 | c.578-53T>C | intron_variant | 1 | P1 | ||||
ALAS1 | ENST00000469224.5 | c.578-53T>C | intron_variant | 1 | P1 | ||||
ALAS1 | ENST00000394965.6 | c.578-53T>C | intron_variant | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.500 AC: 76064AN: 152050Hom.: 19297 Cov.: 34
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GnomAD4 exome AF: 0.523 AC: 699024AN: 1335738Hom.: 184321 AF XY: 0.520 AC XY: 346809AN XY: 667224
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GnomAD4 genome ? AF: 0.500 AC: 76133AN: 152168Hom.: 19313 Cov.: 34 AF XY: 0.496 AC XY: 36916AN XY: 74374
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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