dbSNP rs33925668: NF1:c.6148-18_6148-17delAA (chr17-31336607-TAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001042492.3(NF1):c.6148-18_6148-17delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,307,410 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.877

Publications

2 publications found

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 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

NF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.6148-18_6148-17delAA		intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.6085-18_6085-17delAA		intron	N/A	NP_000258.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NF1	ENST00000358273.9	TSL:1 MANE Select	c.6148-27_6148-26delAA	intron	N/A	ENSP00000351015.4
NF1	ENST00000356175.7	TSL:1	c.6085-27_6085-26delAA	intron	N/A	ENSP00000348498.3
NF1	ENST00000579081.6	TSL:1	n.1313-27_1313-26delAA	intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1307410

Hom.:

AF XY:

0.00000154

AC XY:

AN XY:

648138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27806

American (AMR)

AF:

0.00

AC:

AN:

28856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23382

East Asian (EAS)

AF:

0.00

AC:

AN:

35318

South Asian (SAS)

AF:

0.00

AC:

AN:

73172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4574

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1013868

Other (OTH)

AF:

0.0000370

AC:

AN:

54088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.88

BranchPoint Hunter

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over