chr17-31336607-T-TAA
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_001042492.3(NF1):c.6148-18_6148-17dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,453,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00048 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00094 ( 0 hom. )
Consequence
NF1
NM_001042492.3 intron
NM_001042492.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.877
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 -6 ACMG points.
BP6
?
Variant 17-31336607-T-TAA is Benign according to our data. Variant chr17-31336607-T-TAA is described in ClinVar as [Benign]. Clinvar id is 928871.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 72 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.6148-18_6148-17dup | intron_variant | ENST00000358273.9 | |||
NF1 | NM_000267.3 | c.6085-18_6085-17dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.6148-18_6148-17dup | intron_variant | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000481 AC: 72AN: 149550Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.00150 AC: 210AN: 139834Hom.: 3 AF XY: 0.00156 AC XY: 118AN XY: 75790
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GnomAD4 exome AF: 0.000942 AC: 1228AN: 1303450Hom.: 0 Cov.: 33 AF XY: 0.000927 AC XY: 599AN XY: 646184
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 02, 2019 | Variant summary: NF1 c.6085-18_6085-17dupAA alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0015 in 139834 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 600 fold of the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.6085-18_6085-17dupAA in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at