1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGAGAGAGAGA
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1
The NM_000143.4(FH):c.1237-14_1237-13delTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,479,644 control chromosomes in the GnomAD database, including 99 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000143.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FH | NM_000143.4 | c.1237-14_1237-13delTC | intron_variant | Intron 8 of 9 | ENST00000366560.4 | NP_000134.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0219 AC: 2928AN: 133722Hom.: 96 Cov.: 0
GnomAD4 exome AF: 0.0408 AC: 54855AN: 1345834Hom.: 3 AF XY: 0.0412 AC XY: 27588AN XY: 669888
GnomAD4 genome AF: 0.0220 AC: 2939AN: 133810Hom.: 96 Cov.: 0 AF XY: 0.0219 AC XY: 1396AN XY: 63822
ClinVar
Submissions by phenotype
Hereditary leiomyomatosis and renal cell cancer Uncertain:2
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not provided Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Fumarase deficiency Uncertain:1
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not specified Benign:1
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FH-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at