rs8072417
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001042492.3(NF1):c.4578-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,611,076 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0095 ( 23 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 24 hom. )
Consequence
NF1
NM_001042492.3 intron
NM_001042492.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.70
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 17-31261672-A-G is Benign according to our data. Variant chr17-31261672-A-G is described in ClinVar as [Benign]. Clinvar id is 257291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00949 (1446/152316) while in subpopulation AFR AF= 0.0328 (1362/41550). AF 95% confidence interval is 0.0313. There are 23 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1446 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.4578-39A>G | intron_variant | ENST00000358273.9 | |||
NF1 | NM_000267.3 | c.4515-39A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.4578-39A>G | intron_variant | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00947 AC: 1442AN: 152198Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.00236 AC: 592AN: 251194Hom.: 9 AF XY: 0.00159 AC XY: 216AN XY: 135774
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GnomAD4 exome AF: 0.00102 AC: 1487AN: 1458760Hom.: 24 Cov.: 30 AF XY: 0.000860 AC XY: 624AN XY: 725742
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GnomAD4 genome ? AF: 0.00949 AC: 1446AN: 152316Hom.: 23 Cov.: 32 AF XY: 0.00929 AC XY: 692AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 26, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Neurofibromatosis, familial spinal Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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