rs1555614386

Variant names:

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The ENST00000358273.9(NF1):c.2990_2990+1insGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTAGGGTACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAG variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

NF1
ENST00000358273.9 splice_donor, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.188

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-31229679-T-TGGGTACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAGGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTA is Pathogenic according to our data. Variant chr17-31229679-T-TGGGTACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAGGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTA is described in ClinVar as [Pathogenic]. Clinvar id is 217110.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3 link	c.2851-151_2990+121dupACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAGGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTAGGGT		intron_variant	Intron 22 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 link	c.2851-151_2990+121dupACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAGGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTAGGGT		intron_variant	Intron 22 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.2990_2990+1insGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTAGGGTACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAG		splice_donor_variant, intron_variant	Intron 22 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

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

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over