chr16-31185093-CGGCGGCGGT-C
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1
The NM_004960.4(FUS):c.681_689delCGGCGGTGG(p.Gly228_Gly230del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000156 in 1,605,334 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
FUS
NM_004960.4 disruptive_inframe_deletion
NM_004960.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.91
Genes affected
FUS (HGNC:4010): (FUS RNA binding protein) This gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. The hnRNP complex is involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm. This protein belongs to the FET family of RNA-binding proteins which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. Alternative splicing results in multiple transcript variants. Defects in this gene result in amyotrophic lateral sclerosis type 6. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
Variant 16-31185093-CGGCGGCGGT-C is Benign according to our data. Variant chr16-31185093-CGGCGGCGGT-C is described in ClinVar as [Likely_benign]. Clinvar id is 447358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00016 (233/1453558) while in subpopulation MID AF= 0.00087 (5/5750). AF 95% confidence interval is 0.000351. There are 1 homozygotes in gnomad4_exome. There are 133 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 151658Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000178 AC: 41AN: 230104Hom.: 0 AF XY: 0.000231 AC XY: 29AN XY: 125510
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GnomAD4 exome AF: 0.000160 AC: 233AN: 1453558Hom.: 1 AF XY: 0.000184 AC XY: 133AN XY: 722660
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GnomAD4 genome AF: 0.000112 AC: 17AN: 151776Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74162
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
FUS-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 26, 2023 | 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). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 16, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2019 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | FUS: BP3 - |
Amyotrophic lateral sclerosis type 6;C3539195:Tremor, hereditary essential, 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 13, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at