chr16-31180220-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_004960.4(FUS):c.6C>T(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,611,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000046 ( 0 hom. )
Consequence
FUS
NM_004960.4 synonymous
NM_004960.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0990
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
?
Variant 16-31180220-C-T is Benign according to our data. Variant chr16-31180220-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3029985.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-31180220-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.099 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FUS | NM_004960.4 | c.6C>T | p.Ala2= | synonymous_variant | 1/15 | ENST00000254108.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FUS | ENST00000254108.12 | c.6C>T | p.Ala2= | synonymous_variant | 1/15 | 1 | NM_004960.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000289 AC: 7AN: 242018Hom.: 0 AF XY: 0.0000228 AC XY: 3AN XY: 131460
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GnomAD4 exome AF: 0.0000459 AC: 67AN: 1458898Hom.: 0 Cov.: 35 AF XY: 0.0000455 AC XY: 33AN XY: 725574
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74354
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FUS-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 15, 2021 | 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
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at