rs886038397

Variant names:

• chr17-31334795-A-ATT
• rs886038397
• NM_001042492.3:c.5813-40_5813-39dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001042492.3(NF1):​c.5813-40_5813-39dupTT variant causes a intron change. The variant allele was found at a frequency of 0.000000765 in 1,306,744 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.78
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
• neurofibromatosis-Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Orphanet
• 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: Unknown 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
• BP6: Variant 17-31334795-A-ATT is Benign according to our data. Variant chr17-31334795-A-ATT is described in ClinVar as Likely_benign. ClinVar VariationId is 257295.Status of the report is criteria_provided_single_submitter, 1 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.5813-40_5813-39dupTT		intron	N/A	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.5750-40_5750-39dupTT		intron	N/A	NP_000258.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.5813-43_5813-42insTT		intron	N/A	ENSP00000351015.4	P21359-1
	NF1	ENST00000356175.7	TSL:1	c.5750-43_5750-42insTT		intron	N/A	ENSP00000348498.3	P21359-2
	NF1	ENST00000579081.6	TSL:1	n.*978-43_*978-42insTT		intron	N/A	ENSP00000462408.2	J3KSB5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.65e-7 AC: 1 AN: 1306744 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 658412

African (AFR) AF: 0.00 AC: 0 AN: 30306

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 38870

South Asian (SAS) AF: 0.00 AC: 0 AN: 82784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5366

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 971934

Other (OTH) AF: 0.0000181 AC: 1 AN: 55284

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

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

Other links and lift over

dbSNP: rs886038397; hg19: chr17-29661813;