1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGA
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_000143.4(FH):c.1237-22_1237-13delTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000912 in 1,490,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000075 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
FH
NM_000143.4 intron
NM_000143.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
FH (HGNC:3700): (fumarate hydratase) The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
Variant 1-241500602-TGAGAGAGAGA-T is Benign according to our data. Variant chr1-241500602-TGAGAGAGAGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2575507.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000929 (126/1356806) while in subpopulation AFR AF= 0.000767 (24/31294). AF 95% confidence interval is 0.000528. There are 0 homozygotes in gnomad4_exome. There are 51 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FH | NM_000143.4 | c.1237-22_1237-13delTCTCTCTCTC | intron_variant | Intron 8 of 9 | ENST00000366560.4 | NP_000134.2 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000747 AC: 10AN: 133802Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.0000929 AC: 126AN: 1356806Hom.: 0 AF XY: 0.0000755 AC XY: 51AN XY: 675462
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GnomAD4 genome 0.0000747 AC: 10AN: 133892Hom.: 0 Cov.: 0 AF XY: 0.000125 AC XY: 8AN XY: 63870
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Mar 04, 2025
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at