Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001042492.3(NF1):c.5813-625_5813-618delTGTGAACC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 20360 hom., cov: 0)

Consequence

NF1
NM_001042492.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.171

Publications

1 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: Benign. The variant received -10 ACMG points.

BP6

Variant 17-31334204-GTGTGAACC-G is Benign according to our data. Variant chr17-31334204-GTGTGAACC-G is described in ClinVar as Benign. ClinVar VariationId is 1288198.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

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.5813-625_5813-618delTGTGAACC		intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.5750-625_5750-618delTGTGAACC		intron	N/A	NP_000258.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NF1	ENST00000358273.9	TSL:1 MANE Select	c.5813-633_5813-626delTGTGAACC	intron	N/A	ENSP00000351015.4
NF1	ENST00000356175.7	TSL:1	c.5750-633_5750-626delTGTGAACC	intron	N/A	ENSP00000348498.3
NF1	ENST00000579081.6	TSL:1	n.978-633_978-626delTGTGAACC	intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

74880

AN:

150916

Hom.:

20354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.682

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.594

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.496

AC:

74906

AN:

151030

Hom.:

20360

Cov.:

AF XY:

0.493

AC XY:

36352

AN XY:

73714

show subpopulations

African (AFR)

AF:

0.276

AC:

11388

AN:

41254

American (AMR)

AF:

0.443

AC:

6727

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

2349

AN:

3446

East Asian (EAS)

AF:

0.356

AC:

1828

AN:

5142

South Asian (SAS)

AF:

0.565

AC:

2704

AN:

4786

European-Finnish (FIN)

AF:

0.599

AC:

6255

AN:

10438

Middle Eastern (MID)

AF:

0.587

AC:

168

AN:

286

European-Non Finnish (NFE)

AF:

0.619

AC:

41791

AN:

67500

Other (OTH)

AF:

0.523

AC:

1099

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1642

3283

4925

6566

8208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.415

Hom.:

1233

Bravo

AF:

0.475

Asia WGS

AF:

0.435

AC:

1509

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs17882240

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over