rs1555614386

Positions:

• chr17-31229679-T-TGGGTACGAGTGTCTGCGTATATCTGTATGCTTATTTGGCTCTATGCCTGTGGGTGCACTTACTCTGTGTGTTTAGATCAGTCAGTTTCATCTCTCTAGGGGGTCTGTCTTCTGGGCATTGATGGCAAATCATTAATGTATTTGTTCTTTCTTTAGGTTTTATTGACTGATACCAATACTCAATTTGTAGAACAAACCATAGCTATAATGAAGAACTTGCTAGATAATCATACTGAAGGCAGCTCTGAACATCTAGGGCAAGCTAGCATTGAAACAATGATGTTAAATCTGGTCAGGTAAGCATTCTACTGAAATGTAGCAGAAACATTTTAAGAGATAAGAAAAACCTCTTACACACTGATACTGGTAGTAATTGATAAAATAACTGGCCATTCTTTACTGCACACAAACTA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001042492.3(NF1):​c.2851-151_2990+121dup variant causes a 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 NM_001042492.3 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.188

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• 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/exons	MANE	UniProt
NF1	NM_001042492.3	c.2851-151_2990+121dup		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.2851-151_2990+121dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.2851-151_2990+121dup		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurofibromatosis, type 1 Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

UAB Medical Genomics Laboratory, UAB Medicine

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555614386; hg19: chr17-29556697;