rs375446476
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The ENST00000358273.9(NF1):c.6642+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,098 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 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NF1
ENST00000358273.9 intron
ENST00000358273.9 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.406
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 -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 17-31337593-C-A is Benign according to our data. Variant chr17-31337593-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1592466.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.6642+11C>A | intron_variant | ENST00000358273.9 | NP_001035957.1 | |||
NF1 | NM_000267.3 | c.6579+11C>A | intron_variant | NP_000258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.6642+11C>A | intron_variant | 1 | NM_001042492.3 | ENSP00000351015 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 151966Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457098Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724978
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 151966Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74222
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurofibromatosis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 09, 2023 | - - |
Computational scores
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Benign
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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