17-31349086-CTTGTTTGTTTGTTTGT-CTTGTTTGTTTGTTTGTTTGT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001042492.3(NF1):c.7190-11_7190-8dupGTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000841 in 1,550,920 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 2 hom. )

Consequence

NF1
NM_001042492.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 4.75

Publications

0 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 17-31349086-C-CTTGT is Benign according to our data. Variant chr17-31349086-C-CTTGT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 560800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0017 (259/152074) while in subpopulation AFR AF = 0.00446 (185/41442). AF 95% confidence interval is 0.00394. There are 0 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 259 AD gene.

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.7190-11_7190-8dupGTTT		splice_region intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.7127-11_7127-8dupGTTT		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.7190-34_7190-33insTTGT	intron	N/A	ENSP00000351015.4
NF1	ENST00000356175.7	TSL:1	c.7127-34_7127-33insTTGT	intron	N/A	ENSP00000348498.3
NF1	ENST00000579081.6	TSL:1	n.2355-34_2355-33insTTGT	intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00443

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000567

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00105

AC:

162

AN:

154686

AF XY:

0.000844

show subpopulations

Gnomad AFR exome

AF:

0.00525

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00192

Gnomad EAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.000710

Gnomad NFE exome

AF:

0.000627

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000748

AC:

1046

AN:

1398846

Hom.:

Cov.:

AF XY:

0.000715

AC XY:

494

AN XY:

690820

show subpopulations

African (AFR)

AF:

0.00512

AC:

162

AN:

31652

American (AMR)

AF:

0.000528

AC:

AN:

36012

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

25190

East Asian (EAS)

AF:

0.000722

AC:

AN:

36008

South Asian (SAS)

AF:

0.000841

AC:

AN:

79654

European-Finnish (FIN)

AF:

0.000420

AC:

AN:

47630

Middle Eastern (MID)

AF:

0.000706

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.000580

AC:

626

AN:

1079004

Other (OTH)

AF:

0.00128

AC:

AN:

58034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

146

194

243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00170

AC:

259

AN:

152074

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00446

AC:

185

AN:

41442

American (AMR)

AF:

0.00111

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.000774

AC:

AN:

5170

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000567

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

67988

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000374

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurofibromatosis, type 1

Benign:3

Nov 06, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

Oct 26, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Mar 29, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30308447, 34426522)

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NF1: BP4, BS1, BS2

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Mar 30, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary cancer-predisposing syndrome

Benign:1

Dec 07, 2021

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.7

Mutation Taster

=19/81

disease causing

(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