17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTT

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.3198-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4359 hom., cov: 0)

Exomes 𝑓: 0.096 ( 2286 hom. )

Consequence

NF1
NM_001042492.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

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-AT is Benign according to our data. Variant chr17-31232043-A-AT is described in ClinVar as Benign. ClinVar VariationId is 803349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 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.3198-4dupT		splice_region intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.3198-4dupT		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_3198-29insT	intron	N/A	ENSP00000351015.4
NF1	ENST00000356175.7	TSL:1	c.3198-30_3198-29insT	intron	N/A	ENSP00000348498.3
NF1	ENST00000579081.6	TSL:1	n.3198-30_3198-29insT	intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

19937

AN:

90834

Hom.:

4358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.0479

Gnomad MID

AF:

0.0561

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.109

AC:

7082

AN:

65012

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.0768

Gnomad EAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0924

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.0963

AC:

47760

AN:

496024

Hom.:

2286

Cov.:

AF XY:

0.105

AC XY:

27331

AN XY:

260534

show subpopulations

African (AFR)

AF:

0.101

AC:

1017

AN:

10078

American (AMR)

AF:

0.156

AC:

2470

AN:

15860

Ashkenazi Jewish (ASJ)

AF:

0.0982

AC:

1197

AN:

12190

East Asian (EAS)

AF:

0.174

AC:

2892

AN:

16652

South Asian (SAS)

AF:

0.159

AC:

6781

AN:

42530

European-Finnish (FIN)

AF:

0.0799

AC:

2297

AN:

28756

Middle Eastern (MID)

AF:

0.0878

AC:

147

AN:

1674

European-Non Finnish (NFE)

AF:

0.0824

AC:

28569

AN:

346556

Other (OTH)

AF:

0.110

AC:

2390

AN:

21728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1117

2234

3352

4469

5586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<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:

0.219

AC:

19935

AN:

90830

Hom.:

4359

Cov.:

AF XY:

0.210

AC XY:

8829

AN XY:

42006

show subpopulations

African (AFR)

AF:

0.220

AC:

4927

AN:

22416

American (AMR)

AF:

0.207

AC:

1534

AN:

7416

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

499

AN:

2610

East Asian (EAS)

AF:

0.303

AC:

823

AN:

2712

South Asian (SAS)

AF:

0.231

AC:

543

AN:

2352

European-Finnish (FIN)

AF:

0.0479

AC:

162

AN:

3380

Middle Eastern (MID)

AF:

0.0575

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.230

AC:

10996

AN:

47866

Other (OTH)

AF:

0.180

AC:

220

AN:

1224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

437

874

1311

1748

2185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0701

Hom.:

224

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurofibromatosis, type 1

Benign:3

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 26, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:1

Aug 11, 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

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

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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