rs786203184
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM4_SupportingBP6BS2_Supporting
The NM_001042492.3(NF1):c.7387_7389delCTT(p.Leu2463del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,614 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001042492.3 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.7387_7389delCTT | p.Leu2463del | conservative_inframe_deletion | Exon 50 of 58 | ENST00000358273.9 | NP_001035957.1 | |
NF1 | NM_000267.3 | c.7324_7326delCTT | p.Leu2442del | conservative_inframe_deletion | Exon 49 of 57 | NP_000258.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251356Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135848
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461430Hom.: 0 AF XY: 0.0000151 AC XY: 11AN XY: 727054
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23047742) -
Neurofibromatosis, type 1;C0349639:Juvenile myelomonocytic leukemia;C0553586:Café-au-lait macules with pulmonary stenosis;C1834235:Neurofibromatosis, familial spinal;C2931482:Neurofibromatosis-Noonan syndrome Uncertain:1
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Hereditary cancer-predisposing syndrome Uncertain:1
The c.7387_7389delCTT variant (also known as p.L2463DEL) located in coding exon 50 of the NF1 gene. This variant results from an in-frame CTT deletion between nucleotide positions 7387 and 7389. This results in the loss of a single leucine residue at codon 2463. In one study, a review of patient reports in the literature, research mutation databases, and unpublished cases described this variant in one individual with a NF1-Noonan syndrome phenotype (<span data-redactor="verified" style="background-color: initial;">Ben-Shachar S et al. Eur. J. Hum. Genet. 2013 May; 21(5):535-9).<span data-redactor="verified" style="background-color: initial;">This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position.<span style="background-color: initial;">To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 11000 alleles tested) in our clinical cohort. <span data-redactor="verified" style="background-color: initial;">This amino acid position is highly conserved in available higher vertebrate species.<span data-redactor="verified" style="background-color: initial;">Since supporting evidence is limited at this time, the clinical significance of<span data-redactor="verified" style="background-color: initial;">c.7387_7389delCTT<span data-redactor="verified" style="background-color: initial;">remains unclear. -
not specified Benign:1
The frequency of this variant in the general population (http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. -
Neurofibromatosis, type 1 Benign:1
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Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at