1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGAGA
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_000143.4(FH):c.1237-20_1237-13delTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,490,680 control chromosomes in the GnomAD database, including 7 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.1237-20_1237-13delTCTCTCTC | intron_variant | Intron 8 of 9 | ENST00000366560.4 | NP_000134.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00436 AC: 584AN: 133804Hom.: 7 Cov.: 0
GnomAD4 exome AF: 0.000753 AC: 1021AN: 1356786Hom.: 0 AF XY: 0.000731 AC XY: 494AN XY: 675456
GnomAD4 genome AF: 0.00437 AC: 585AN: 133894Hom.: 7 Cov.: 0 AF XY: 0.00377 AC XY: 241AN XY: 63870
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
DNA sequence analysis of the FH gene demonstrated a sequence change in intron 8, c.1237-20_1237-13del. This change does not appear to have been previously described in patients with FH-related disorders and has also not been described in population databases (gnomAD, ExAC). This sequence change is not clearly predicted to have a deleterious effect on splicing based on in silico splice prediction programs. It is possible that this sequence change represents a benign sequence change in the FH gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to the disease phenotype cannot definitively be determined. -
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Hereditary cancer-predisposing syndrome 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