chr17-31182783-G-C

Variant names:

• chr17-31182783-G-C
• rs2952999
• NM_001042492.3:c.888+118G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042492.3(NF1):​c.888+118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 10 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10733625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.888+118G>C		intron_variant	Intron 8 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.888+118G>C		intron_variant	Intron 8 of 56		NP_000258.1
NF1	NM_001128147.3	c.888+118G>C		intron_variant	Intron 8 of 14		NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.888+118G>C		intron_variant	Intron 8 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 834088 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 431132

African (AFR) AF: 0.00 AC: 0 AN: 20716

American (AMR) AF: 0.00 AC: 0 AN: 33550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21316

East Asian (EAS) AF: 0.00 AC: 0 AN: 33200

South Asian (SAS) AF: 0.00 AC: 0 AN: 66926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 580820

Other (OTH) AF: 0.00 AC: 0 AN: 39558

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.64
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.11	T
PhyloP100		0.76
GERP RS		-0.90
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2952999; hg19: chr17-29509801;