rs1555613896

Variant names:

• chr17-31227145-G-GAGCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCT
• rs1555613896
• NM_001042492.3:c.2252-70_2326-39dupCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCTAG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_001042492.3(NF1):​c.2252-70_2326-39dupCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCTAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.359
• Publications: 0 publications found

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]

NF1 Gene-Disease associations (from GenCC):

• neurofibromatosis type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
• neurofibromatosis-Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
• Moyamoya disease

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant 17-31227145-G-GAGCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCT is Pathogenic according to our data. Variant chr17-31227145-G-GAGCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCT is described in ClinVar as Pathogenic. ClinVar VariationId is 217109.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.2252-70_2326-39dupCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCTAG		intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.2252-70_2326-39dupCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCTAG		intron	N/A	NP_000258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.2252-73_2252-72insAGCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCT		intron	N/A	ENSP00000351015.4
	NF1	ENST00000356175.7	TSL:1	c.2252-73_2252-72insAGCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCT		intron	N/A	ENSP00000348498.3
	NF1	ENST00000579081.6	TSL:1	n.2252-73_2252-72insAGCTTATCAGGTTCTCCATTGGCAGGCAGGGCTCTAAGTGCAGTAACTTGATTTGCTGTTGTATTTGCTTAGGAAGAGCAGCACTTCAGAAAAGAGTGATGGCACTGCTGAGGCGCATTGAGCATCCCACTGCAGGAAACACTGAGGTATGCCCTTAGCAACAGAAACACCCCTCCCAGGCGCCCACCCTCAATTTGGAAGCCTCTTGTTACATATGTGTGATCAGGAATAGCTTTTGAAGTAAATCCAAGATACGTGCATATTACAAGTATAATATCTGAGTATTTAATATACATCAAGTTTGAAACTTGGCTGTAGCTGATTGATGTTTAGCTCT		intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurofibromatosis, type 1 Pathogenic:1

UAB Medical Genomics Laboratory, UAB Medicine

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=32/68	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555613896; hg19: chr17-29554163;