chr17-31201405-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_001042492.3(NF1):c.1186-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NF1
NM_001042492.3 splice_region, splice_polypyrimidine_tract, intron
NM_001042492.3 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00003714
2
Clinical Significance
Conservation
PhyloP100: -0.243
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 17-31201405-C-T is Benign according to our data. Variant chr17-31201405-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 457522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31201405-C-T is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.1186-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000358273.9 | |||
NF1 | NM_000267.3 | c.1186-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
NF1 | NM_001128147.3 | c.1186-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.1186-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 32AN: 140660Hom.: 0 Cov.: 32 FAILED QC
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GnomAD3 exomes AF: 0.000669 AC: 158AN: 236306Hom.: 0 AF XY: 0.000707 AC XY: 91AN XY: 128662
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000131 AC: 188AN: 1435578Hom.: 0 Cov.: 30 AF XY: 0.000132 AC XY: 94AN XY: 713928
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000227 AC: 32AN: 140660Hom.: 0 Cov.: 32 AF XY: 0.000220 AC XY: 15AN XY: 68040
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
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 | Jan 05, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Neurofibromatosis, type 1;C0349639:Juvenile myelomonocytic leukemia;C0553586:Café-au-lait macules with pulmonary stenosis;C1834235:Neurofibromatosis, familial spinal;C2931482:Neurofibromatosis-Noonan syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 18, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 27, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at