1-241506178-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000143.4(FH):c.739-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,600,856 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000143.4 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FH | NM_000143.4 | c.739-10T>C | intron_variant | Intron 5 of 9 | ENST00000366560.4 | NP_000134.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000688 AC: 167AN: 242878Hom.: 1 AF XY: 0.000859 AC XY: 113AN XY: 131508
GnomAD4 exome AF: 0.000295 AC: 428AN: 1448498Hom.: 4 Cov.: 27 AF XY: 0.000416 AC XY: 300AN XY: 721216
GnomAD4 genome AF: 0.000223 AC: 34AN: 152358Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74516
ClinVar
Submissions by phenotype
Hereditary leiomyomatosis and renal cell cancer Benign:4
This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
- -
- -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:3
- -
- -
- -
not provided Benign:2
- -
- -
Fumarase deficiency Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at