rs780145472
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting
The NM_001042492.3(NF1):c.5769G>A(p.Thr1923=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,630 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
NF1
NM_001042492.3 synonymous
NM_001042492.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.581
Genes affected
NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 17-31330455-G-A is Benign according to our data. Variant chr17-31330455-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 457762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.581 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 13 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.5769G>A | p.Thr1923= | synonymous_variant | 39/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.5706G>A | p.Thr1902= | synonymous_variant | 38/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.5769G>A | p.Thr1923= | synonymous_variant | 39/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251144Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135726
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461548Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727084
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74290
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Neurofibromatosis, type 1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | NF1: BP4, BP7 - |
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