rs864622331
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001042492.3(NF1):c.-8G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,384,802 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
NF1
NM_001042492.3 5_prime_UTR
NM_001042492.3 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.78
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 Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 17-31095302-G-A is Benign according to our data. Variant chr17-31095302-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 219977.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.-8G>A | 5_prime_UTR_variant | 1/58 | ENST00000358273.9 | ||
NF1 | NM_000267.3 | c.-8G>A | 5_prime_UTR_variant | 1/57 | |||
NF1 | NM_001128147.3 | c.-8G>A | 5_prime_UTR_variant | 1/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.-8G>A | 5_prime_UTR_variant | 1/58 | 1 | NM_001042492.3 | P1 | ||
MIR4733HG | ENST00000583377.1 | n.149C>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 genomes
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30
GnomAD3 exomes AF: 0.00000755 AC: 1AN: 132458Hom.: 0 AF XY: 0.0000138 AC XY: 1AN XY: 72252
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GnomAD4 exome AF: 0.00000217 AC: 3AN: 1384802Hom.: 0 Cov.: 33 AF XY: 0.00000439 AC XY: 3AN XY: 683252
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GnomAD4 genome Cov.: 30
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2015 | - - |
NF1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 12, 2022 | 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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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