17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001042492.3(NF1):c.3198-5_3198-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 249 hom., cov: 0)

Exomes 𝑓: 0.039 ( 382 hom. )

Consequence

NF1
NM_001042492.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.50

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: Benign. The variant received -16 ACMG points.

BP6

Variant 17-31232043-A-ATT is Benign according to our data. Variant chr17-31232043-A-ATT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 996535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 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.3198-5_3198-4dupTT		splice_region intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.3198-5_3198-4dupTT		splice_region intron	N/A	NP_000258.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NF1	ENST00000358273.9	TSL:1 MANE Select	c.3198-30_3198-29insTT	intron	N/A	ENSP00000351015.4
NF1	ENST00000356175.7	TSL:1	c.3198-30_3198-29insTT	intron	N/A	ENSP00000348498.3
NF1	ENST00000579081.6	TSL:1	n.3198-30_3198-29insTT	intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

1986

AN:

90884

Hom.:

250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.00498

Gnomad EAS

AF:

0.0246

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.00118

Gnomad MID

AF:

0.00510

Gnomad NFE

AF:

0.00733

Gnomad OTH

AF:

0.0197

GnomAD2 exomes

AF:

0.0492

AC:

3200

AN:

65012

AF XY:

0.0484

show subpopulations

Gnomad AFR exome

AF:

0.0860

Gnomad AMR exome

AF:

0.0925

Gnomad ASJ exome

AF:

0.0314

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.00480

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0544

GnomAD4 exome

AF:

0.0394

AC:

19552

AN:

496486

Hom.:

382

Cov.:

AF XY:

0.0428

AC XY:

11174

AN XY:

260774

show subpopulations

African (AFR)

AF:

0.0495

AC:

500

AN:

10096

American (AMR)

AF:

0.0714

AC:

1138

AN:

15932

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

418

AN:

12192

East Asian (EAS)

AF:

0.0639

AC:

1064

AN:

16664

South Asian (SAS)

AF:

0.0797

AC:

3401

AN:

42698

European-Finnish (FIN)

AF:

0.0296

AC:

852

AN:

28762

Middle Eastern (MID)

AF:

0.0319

AC:

AN:

1664

European-Non Finnish (NFE)

AF:

0.0323

AC:

11207

AN:

346748

Other (OTH)

AF:

0.0423

AC:

919

AN:

21730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

511

1023

1534

2046

2557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0219

AC:

1987

AN:

90880

Hom.:

249

Cov.:

AF XY:

0.0219

AC XY:

920

AN XY:

42032

show subpopulations

African (AFR)

AF:

0.0610

AC:

1368

AN:

22440

American (AMR)

AF:

0.0163

AC:

121

AN:

7430

Ashkenazi Jewish (ASJ)

AF:

0.00498

AC:

AN:

2612

East Asian (EAS)

AF:

0.0251

AC:

AN:

2710

South Asian (SAS)

AF:

0.0157

AC:

AN:

2352

European-Finnish (FIN)

AF:

0.00118

AC:

AN:

3380

Middle Eastern (MID)

AF:

0.00575

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00733

AC:

351

AN:

47878

Other (OTH)

AF:

0.0196

AC:

AN:

1226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00571

Hom.:

224

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurofibromatosis, type 1

Benign:2

Oct 26, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Aug 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over