rs1370275
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000137.4(FAH):c.82-13G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,604,670 control chromosomes in the GnomAD database, including 215,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.46 ( 17032 hom., cov: 31)
Exomes 𝑓: 0.52 ( 198177 hom. )
Consequence
FAH
NM_000137.4 splice_polypyrimidine_tract, intron
NM_000137.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.70
Genes affected
FAH (HGNC:3579): (fumarylacetoacetate hydrolase) Predicted to enable fumarylacetoacetase activity. Predicted to be involved in L-phenylalanine catabolic process; homogentisate catabolic process; and tyrosine catabolic process. Predicted to act upstream of or within arginine catabolic process. Located in extracellular exosome. Implicated in tyrosinemia type I. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BP6
?
Variant 15-80158047-G-A is Benign according to our data. Variant chr15-80158047-G-A is described in ClinVar as [Benign]. Clinvar id is 92446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-80158047-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAH | NM_000137.4 | c.82-13G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000561421.6 | |||
FAH | NM_001374377.1 | c.82-13G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
FAH | NM_001374380.1 | c.82-13G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAH | ENST00000561421.6 | c.82-13G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000137.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.461 AC: 69992AN: 151768Hom.: 17037 Cov.: 31
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GnomAD3 exomes AF: 0.511 AC: 128519AN: 251430Hom.: 34418 AF XY: 0.522 AC XY: 70912AN XY: 135886
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GnomAD4 exome AF: 0.517 AC: 751629AN: 1452784Hom.: 198177 Cov.: 30 AF XY: 0.521 AC XY: 376826AN XY: 723388
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GnomAD4 genome ? AF: 0.461 AC: 70017AN: 151886Hom.: 17032 Cov.: 31 AF XY: 0.461 AC XY: 34185AN XY: 74222
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Tyrosinemia type I Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 26, 2019 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 25, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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